Blended extended depth of focus light adjustable lens with laterally offset axes

ABSTRACT

A Light Adjustable Lens (LAL) comprises a central region, centered on a central axis, having a position-dependent central optical power, and a peripheral annulus, centered on an annulus axis and surrounding the central region, having a position-dependent peripheral optical power; wherein the central optical power is at least 0.5 diopters different from an average of the peripheral optical power, and the central axis is laterally shifted relative to the annulus axis. A method of adjusting the LAL comprises implanting a LAL; applying a first illumination to the LAL with a first illumination pattern to induce a position-dependent peripheral optical power in at least a peripheral annulus, centered on an annulus axis; determining a central region and a corresponding central axis of the LAL; and applying a second illumination to the LAL with a second illumination pattern to induce a position-dependent central optical power in the central region of the LAL.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a Continuation-In-Part of U.S. patentapplication Ser. No. 13/488,099, entitled “Using the light adjustablelens (LAL) to increase the depth of focus by inducing targeted amountsof asphericity”, by C. A. Sandstedt, P. Artal, and E. Angel Villegas,filed on Jun. 4, 2012, that claims priority from and benefit ofprovisional application 61/535,793, filed on Sep. 16, 2011, the entirecontent of both applications hereby incorporated by reference in theirentirety.

TECHNICAL FIELD

The field of the invention includes at least medical and surgicalinstruments; treatment devices; surgery and surgical supplies; and,medicine. In general, the field of subject matter of the inventionincludes ophthalmology. More specifically, the disclosure relates tooptical elements, which can be modified post-manufacture such thatdifferent versions of the element will have different opticalproperties. In particular, the disclosure relates to lenses, such asintraocular lenses, which can be converted into aspheric lensespost-fabrication. This invention relates to light adjustable lenses witha depth of focus, and more specifically to blended extended depth offocus light adjustable lenses and to the methods of adjusting theselenses by illumination.

BACKGROUND

An intraocular lens (IOL) is a surgically implanted, polymeric lensdesigned to replace the natural crystalline lens in the human eye,typically in patients who have developed visually significant cataracts.Since their inception in the late 1940's, IOLs have provided improveduncorrected visual acuity (UCVA) compared to that of the cataractous oraphakic state; however, problems in predictably achieving emmetropiapersist as most post-cataract surgery patients rely on spectacles orcontact lenses for optimal distance vision. Compounding the issuesrelated to achieving optimum distance vision, patients undergoingcataract surgery lose their ability to accommodate, i.e. the ability tosee objects at both near and distance.

The determination of IOL power required for a particular post-operativerefraction is dependent on the axial length of the eye, the opticalpower of the cornea, and the predicted location of the IOL within theeye. Accurate calculation of IOL power is difficult because thedetermination of axial length, corneal curvature, and the predictedposition of the JOL in the eye is inherently inaccurate. (Narvaez etal., 2006; Olsen, 1992; Preussner et al., 2004; Murphy ei al., 2002).Surgically induced cylinder and variable lens position followingimplantation will create refractive errors, even if preoperativemeasurements were completely accurate, (Olsen, 1992) Currently, theoptions for IOL patients with less than optimal uncorrected visionconsist ofpost-operative correction with spectacles, contact lenses orrefractive surgical procedures. Because IOL exchange procedures carrysignificant risk, secondary surgery to remove the IOL and replace thefirst IOL with a different power IOL is generally limited to severepost-operative refractive errors.

With current methods of IOL power determination, the vast majority ofpatients achieve a UCVA of 20/40 or better. A much smaller percentageachieves optimal vision without spectacle correction. Nearly allpatients are within two diopters (D) of emmetropia.

In a study of 1,676 patients, 1,569 (93.6%) patients were within twodiopters of the intended refractive outcome. (Murphy el al., 2002). In1,320 cataract extractions on patients without ocular co-morbidity,Murphy and co-workers found that 858 (65%) had uncorrected visual acuitygreater than 20/40. (Murphy el al., 2002). A 2007 survey of cataractsurgeons reported that incorrect IOL power remains a primary indicationfor foldable IOL explantation or exchange. (Mamalis et al., 2008; andJin et al., 2007)

In addition to imprecise IOL power determinations, post-operativeuncorrected visual acuity is most often limited by pre-existingastigmatism. Staar Surgical (Monrovia, Calif.) and Alcon Laboratories(Ft. Worth, Tex.) both market a toric IOL that corrects pre-existingastigmatic errors. These IOLs are available in only two to three toricpowers (2.0, 3.5 D and 1.50, 2.25 and 3.0 D, respectively at the IOLplane) and the axis must be precisely aligned at surgery. Other thansurgical repositioning, there is no option to adjust the IOL's axiswhich may shift post-operatively. (Sun el al., 2000) Furthermore;individualized correction of astigmatism is limited by theunavailability of multiple toric powers.

An additional problem associated with using pre-implantation cornealastigmatic errors to gauge the required axis and power of a toric IOL isthe unpredictable effect of surgical wound healing on the finalrefractive error. After the refractive effect of the cataract woundstabilizes, there is often a shift in both magnitude and axis ofastigmatism which off-sets the corrective effect of a toric IOL.Therefore, a means to post-operatively adjust (correct) astigmaticrefractive errors after lens implantation and surgical wound healing isvery desirable. While limbal relaxing incision is a widely acceptedtechnique for treating corneal astigmatism, the procedure, is typicallyperformed during cataract surgery; therefore, the procedure does notaddress the effect of post-implantation wound healing.

In the United States alone, approximately one million eyes undergocorneal refractive procedures which subsequently develop cataracts,thus, presenting a challenge with respect to JOL power determination.Corneal topographic alterations induced by refractive surgery reduce theaccuracy of keratometric measurements, often leading to significantpost-operative ametropia. (Feiz el al., 2005; Wang et al., 2004; Latkanyet al., 2005; Mackool e al., 2006; Packer et al., 2004; Fam and Lim,2008; Chokshi et al., 2007; Camellin and Calossi, 2006). Recent studiesof patients who have had corneal refractive surgery (photorefractivekeratectomy, laser in situ keratomileusis, radial keratotomy) andsubsequently required cataract surgery frequently demonstrate refractive“surprises” post-operatively. As the refractive surgery population agesand develops cataracts, appropriate selection of IOL power fobr thesepatients has become an increasingly challenging clinical problem. Theability to address this problem with an adjustable IOL is valuable topatients seeking optimal distance vision after cataract surgery.

Accommodation, as it relates to the human visual system, refers to theability of a person to use their unassisted ocular structure to viewobjects at both near (e.g. reading) and far (e.g. driving) distances.The mechanism whereby humans accommodate is by contraction andrelaxation of the ciliary body, which connects onto the capsular bagsurrounding the natural lens. Under the application of ciliary stress,the human lens will undergo a shape change effectively altering theradius of curvature of the lens. (Ciuffreda, 1998). This action producesa concomitant change in the power of the lens. However, as people growolder the ability for their eyes to accommodate reduces dramatically.This condition is known as presbyopia and currently affects more than 90million people in the United States. The most widely accepted theory toexplain the loss of accommodation was put forth by Helmholtz. Accordingto Helmholtz, as the patient ages, the crystalline lens of the human eyebecomes progressively stiffer prohibiting deformation under the appliedaction of the ciliary body. (Helmholtz, 1969). People who can seeobjects at a distance without the need for spectacle correction, buthave lost the ability to see objects up close are usually prescribed apair of reading glasses or magnifiers. For those patients who haverequired previous spectacle correction due to preexisting defocus and/orastigmatism, they are prescribed a pair of bifocals, trifocals,variable, or progressive focus lenses which allows the person to haveboth near and distance vision. Compounding this condition is the risk ofcataract development as the patient ages.

To effectively treat both presbyopia and cataracts, the patient can beimplanted with a multifocal IOL. The two most widely adopted multifocalIOLs currently sold in the United States are the ReZoom (Abbott MedicalOptics, Santa Ana, Calif.) and ReStor® (Alcon, Fort Worth, Tex.) lenses.The ReZoom® lens is comprised of five concentric, aspheric refractivezones. (U.S. Pat. No. 5,225,858). Each zone is a multifocal element andthus pupil size should play little or no role in determining final imagequality. However, the pupil size must be greater than 2.5 mm to be ableto experience the multifocal effect. Image contrast is sacrificed at thenear and far distances, to achieve the intermediate and has anassociated loss equivalent to one line of visual acuity. (Steiner elal., 1999). The ReStore lenses, both the 3.0 and 4.0 versions, providesimultaneous near and distance vision by a series of concentric,apodized diffractive rings in the central, three millimeter diameter ofthe lenses. The mechanism of diffractive optics should minimize theproblems associated with variable pupil sizes and small amounts ofdecentration. The acceptance and implantation of both of these lenseshas been limited by the difficulty experienced with glares, rings,halos, monocular diplopia, and the contraindication for patients with anastigmatism of greater than or equal to 2.0 D. (Hansen el al., 1990;and, Ellingson, 1990). Again precise, preoperative measurements andaccurate IOL power calculations are critical to the success of therefractive outcome, and neither the ReZoom nor the ReStor lenses providean opportunity for secondary power adjustment post implantation. (Packeret al., 2002).

One of the newest concepts proposed to tackle the dual problems ofcataracts and presbyopia are through the use of accommodating IOLs. Twocompanies, Bausch & Lomb (Rochester, N.Y.) and Human Optics AG(Erlangen, Germany) have developed IOLs that attempt to take advantageof the existing accommodative apparatus of the eye in post implantationpatients to treat presbyopia. Bausch & Lomb's lens offers a plate hapticconfigured IOL with a flexible hinged optic (CrystaLens®). HumanOptics's lens (AKKOMMODATIVE® ICU) is similar in design, but possessesfour hinged haptics attached to the edge of the optic. The accommodativeeffect of these lenses is caused by the vaulting of the plate IOL by thecontraction of the ciliary body. This vaulting may be a response of theciliary body contraction directly or caused by the associated anteriordisplacement of the vitreous body. Initial reports of the efficacy ofthese two lenses in clinical trials was quite high with dynamicwavefront measurement data showing as much as 2 D to 3 D (measured atthe exit pupil of the eye) of accommodation. However, the FDA OphthalmicDevices' panel review of Bausch & Lomb's clinical results concluded thatonly a 1 D accommodative response (at the spectacle plane) wassignificantly achieved by their lens, which is nearly identical to thepseudo-accommodation values achieved for simple monofocal IOLs.

A need exists for an intraocular lens which is adjusted post operativelyin-vivo to form a presbyopia correcting intraocular lens. This type oflens can be designed in-vivo to correct to an initial emmetropic state(light from infinity forming a perfect focus on the retina) and then thepresbyopia correction is added during a second treatment. Such a lenswould (1) remove the guess work involved in presurgical power selection,(2) overcome the wound healing response inherent to IOL implantation,and (3) allow the amount of near vision to be customized to correspondto the patient's requirements. Also, an intraocular lens which isadjusted post operatively in-vivo to form an aspheric optical elementwould result in the patient having an increased depth of focus (DOF),which allows the patient to see both distance and near (e.g. 40 cm)through the same lens.

The techniques of cataract surgery are progressing at an impressivepace. Generations of phacoemulsification platforms and more recentlyintroduced surgical lasers keep increasing the precision of theplacement of intraocular lenses (IOLs) and keep reducing unintendedmedical outcomes. Nevertheless, after the IOLs have been implanted, thepostsurgical healing process can shift or tilt the IOLs in a notablefraction of the patients, leading to a diminished visual acuity, and adeviation from the planned surgical outcome.

A new technique has been developed recently to correct or mitigate suchpostsurgical IOL shift or tilt. This new technique is capable ofadjusting the optical properties of the IOLs with a postsurgicalprocedure to compensate the shift or tilt of the IOL. As describedelsewhere in this patent document and in commonly owned U.S. Pat. No.6,905,641, to Platt et al, entitled: “Delivery system for post-operativepower adjustment of adjustable lens”, hereby incorporated by referencein its entirety, the IOLs can be fabricated from a photo-polymerizablematerial, henceforth making them Light Adjustable Lenses, or LALs. Inthe days after the surgery, the implanted LALs may shift and tilt,eventually settling into a postsurgical position different from what thesurgeon planned. At this time, a Light Delivery System (LDD) can be usedto illuminate the LALs with an illumination pattern that induces achange in the refractive properties of the LALs, such that their opticalperformance is modified to compensate the unintended postsurgical shiftor tilt of the LAL.

Some existing IOLs have a radially varying optical power. Their opticalperformance is characterized by an extended depth of focus (EDOF), andthereby can be helpful to mitigate presbyopia in patients. Some of theseEDOF IOLs are pre-formed before implantation. Alternatively, theradially varying optical power can be induced by applying a radiallyvarying illumination pattern after the LAL was implanted and thensettled, as described elsewhere in this document. While the medicalbenefit of the EDOF IOLs is substantial, the effective optical power ofthese EDOF IOLs varies with the radius of the pupil of the eye. Thus, aslight conditions vary, such as when transitioning from an indoorenvironment to outdoors, as the pupil adapts to the transition, theoptical performance of such EDOF IOLs/LALs changes, which can bechallenging to adapt to for a notable fraction of patients. Also, sincethese EDOF IOLs/LALs have an extended focal region instead of a sharplydefined focal point, the image they create on the retina is experiencedby some patients as having some aberrations, being somewhat blurry.

Another class of presbyopia-mitigating IOLs has been described in thecommonly owned U.S. Pat. No. 7,281,795, to Sandstedt et al., entitled:“Light adjustable multifocal lenses”, hereby incorporated by referencein its entirety. This class of IOLs have a central region with a centraloptical power and corresponding central focal point, and a peripheralregion with a peripheral optical power and corresponding peripheralfocal point. Accordingly, these are sometimes referred to as multifocalIOLs. Typically, the central region is formed for near vision and theperipheral region for distance vision. Accordingly, the central opticalpower is typically 1-3 diopters stronger than the peripheral opticalpower. The central region is sometimes referred to as a “Central NearAdd” (CNA) region. As with EDOF IOLs, multifocal IOLs can also be eitherpre-formed prior to the surgery, or can be formed post-surgically, byapplying an appropriate illumination pattern to an implanted LAL.

These CNA, or multifocal IOLs have the potential to mitigate presbyopiasimilarly to multifocal contact lenses. One of the medical benefits ofthese multifocal lenses is that their focal points are well-defined.Therefore, the images they form at the focal points have only smallaberrations. At the same time, one of the challenges of multifocal IOLsis that the visual acuity strongly depends on how precisely the CNAregion is aligned with the visual axis of the eye. Even a smalldecentering of the small CNA region can induce various aberrations andastigmatism, most notably coma, and thus can cause a substantialdeterioration of the visual acuity. Since the CNA region is typicallyquite small, and the implanted multifocal IOLs also tend to shift andtilt, the visual acuity of the pre-formed multifocal IOLs oftendeteriorates as they shift and de-center after implantation.

There are several possible sources of decentering. In cases, where thecentral region is formed prior to implantation, such as molded into anIOL, or into a LAL, the postsurgical shifts of the IOL/LAL can lead to acorrespondingly decentered central region. In cases, where the centralregion is formed after the implantation by illuminating the LAL with asuitable illumination pattern, another issue can lead to the sameproblem. The LALs are illuminated after the iris of the eye issubstantially dilated, in order to accommodate the entire illuminationpattern. In some cases, the illumination pattern to form the CNA regioncan be centered on the geometric axis of the LAL. Less typically, theillumination pattern can be centered on the dilated iris. In eithercase, subsequently the iris often returns to its natural, non-dilatedstate non-symmetrically, thus shifting the visual axis of the eye. Thus,the CNA region that was centered either on the geometric LAL axis, or onthe dilated iris, may end up being notably decentered from the visualaxis of the eye, defined by the non-dilated iris.

The problematic visual acuity of the decentered central CNA region isprobably one of the causes why existing CNA/multifocal IOLs achievedonly limited market acceptance. It is mentioned that the Central NearAdd concept has been also implemented in related ophthalmictechnologies: as implanted small corneal inlays, and as CNA contactlenses. These technologies also suffer from the analogous problem ofpostsurgical shift and decentration.

For at least the above reasons, there is a pressing medical need for thefollowing improvement in the field of presbyopia-mitigating IOLs/LALs.(1) A new class of IOLs/LALs that deliver the presbyopia-mitigatingmedical benefits of the EDOF and the CNA/multifocal designs, whilelimiting or minimizing the undesirable aspects of their opticalperformance. (2) LALs/IOLs, whose CNA region is aligned with the visualaxis of the eye in the non-dilated state of the iris.

SUMMARY

General embodiments of the present invention provide a first opticalelement whose properties may be adjusted post-manufacture to produce asecond optical element, wherein the second optical element is capable ofproviding an increased depth of focus to a patient. Specifically, theinvention relates to a spherical intraocular lens that is capable ofbeing transformed post-operatively into an aspheric optical element.Through this approach, the intraocular and/or focal zones of theaspheric optical element can be more precisely adjusted after the lenshas been subjected to any post-operative migration. Also, the adjustmentof the aspheric optical element can be based on input from the patientand/or the adjustment of the aspheric optical element can beaccomplished through standard refraction techniques rather than makingthe adjustment through preoperative estimation.

The alteration of the spherical IOL is accomplished via a modifyingcomposition (“MC”) dispersed throughout the spherical IOL. The MC iscapable of polymerization when exposed to an external stimulus such asheat or light. The stimulus can be directed to one or more regions ofthe element causing polymerization of the MC only in the exposedregions. The polymerization of the MC causes changes in the opticalproperties of the element within the exposed regions. In someembodiments, the optical properties changed though the polymerization ofthe MC include a change in the radius of curvature and/or a change inthe refractive index.

The method for providing an aspheric lens begins with the formation ofthe first polymer matrix in the presence of the modifying composition.The next step is the formation of a second polymer matrix comprisingpolymerized MC. The formation of this polymer network changes theoptical properties of the element, namely the refractive index. Inaddition, when the MC is polymerized to form the second polymer matrix,a gradient or a difference in the chemical potential between thepolymerized and unpolymerized regions is induced. This in turn causesthe unpolymerized MC to diffuse within the element, which reestablishesa thermodynamic equilibrium within the optical element. If the opticalelement possesses sufficient elasticity, this migration of MC can causeswelling of the element in the area exposed to the stimulus. This, inturn, changes the shape of the element, causing changes in the opticalproperties (i.e., radius of curvature and/or refractive index). Whetherthe radius of curvature of the element and/or the refractive index ofthe element change depends upon (1) the nature of the optical element,(2) the MC incorporated into the element, (3) the duration that theelement is exposed to a stimulus, and (4) the spatial intensity profileof the stimulus.

By controlling the radiant exposure (i.e., beam irradiance andduration), spatial irradiance profile, and target area, physical changesin the radius of curvature of the lens surface are achieved, therebymodifying the refractive power of an implanted lens (1) to correctspherical refractive errors, (2) to correct sphero-cylindricalrefractive errors, (3) to induce a targeted amount of asphericity and/ora combination thereof. Once the appropriate refractive adjustment isachieved, the entire aspheric lens is irradiated to polymerize theremaining unreacted MC under conditions that prevent any additionalchange in lens power. By irradiating the entire lens, MC diffusion isprevented thus no change in lens power results. This second irradiationprocedure is referred to as “lock-in”.

In another aspect of the present invention, the optical elements areself-contained in that once fabricated, no material is either added orremoved from the lens to obtain the desired optical properties.

The above described medical needs are further addressed by the followingembodiments of Light Adjustable Lenses. Some embodiments of a LightAdjustable Lens (LAL) can comprise a central region, centered on acentral axis, having a position-dependent central optical power, and; aperipheral annulus, centered on an annulus axis and surrounding thecentral region, having a position-dependent peripheral optical power;wherein an average of the central optical power is at least 0.5 dioptersdifferent from an average of the peripheral optical power, and thecentral axis is laterally shifted relative to the annulus axis.

In some embodiments, a Light Adjustable Lens (LAL) comprises alight-adjusted region, centered on an adjustment axis and having aposition-dependent optical power; wherein the adjustment axis islaterally shifted relative to a LAL axis of the LAL.

In some embodiments, a method of adjusting a Light Adjustable Lens (LAL)comprises the steps of: implanting a LAL into an eye; applying a firstillumination to the LAL with a first illumination pattern to induce aposition-dependent peripheral optical power in at least a peripheralannulus, centered on an annulus axis; determining a central region and acorresponding central axis of the LAL; and applying a secondillumination to the LAL with a second illumination pattern to induce aposition-dependent central optical power in the central region of theLAL; wherein the central axis is laterally shifted relative to theannulus axis, and an average of the central optical power is at least0.5 diopters different from than an average of the peripheral opticalpower.

In some embodiments, a method of adjusting a Light Adjustable Lens (LAL)comprises the steps of: implanting a LAL into an eye, the LAL having apre-molded position-dependent peripheral optical power in at least aperipheral annulus, centered on an annulus axis; determining a centralregion and a corresponding central axis of the LAL; and applying acentral illumination to the LAL with a central illumination pattern toinduce a position-dependent central optical power in the central regionof the LAL; wherein the central axis is laterally shifted relative tothe annulus axis, and an average of the central optical power is atleast 0.5 diopters different from than an average of the peripheraloptical power.

In some embodiments, a method of adjusting a Light Adjustable Lens (LAL)comprises the steps of: implanting a LAL, having a LAL axis, into aneye; and applying an illumination to the LAL with an illuminationpattern to induce a position-dependent optical power in a light-adjustedregion, centered on an adjustment axis; wherein the adjustment axis islaterally shifted relative to the LAL axis.

In some embodiments, a method of adjusting a Light Adjustable Lens (LAL)comprises the steps of: causing an LAL, implanted into an eye, to inducea first depth of focus of the ophthalmic optical system; determining acentral region and a corresponding central axis of the LAL; andilluminating the LAL with an illumination pattern centered on thecentral axis to induce a second depth of focus of the ophthalmic opticalsystem; wherein the central axis is laterally shifted relative to a LALaxis, and the second depth of focus is at least 0.5 diopters greaterthan the first depth of focus.

The foregoing has outlined rather broadly the features and technicaladvantages of the present invention in order that the detaileddescription of the invention that follows may be better understood.Additional features and advantages of the invention will be describedhereinafter which form the subject of the claims of the invention. Itshould be appreciated by those skilled in the art that the conceptionand specific embodiment disclosed may be readily utilized as a basis formodifying or designing other structures for carrying out the samepurposes of the present invention. It should also be realized by thoseskilled in the art that such equivalent constructions do not depart fromthe spirit and scope of the invention as set forth in the appendedclaims. The novel features which are believed to be characteristic ofthe invention, both as to its organization and method of operation,together with further objects and advantages will be better understoodfrom the following description when considered in connection with theaccompanying figures. It is to be expressly understood, however, thateach of the figures is provided for the purpose of illustration anddescription only and is not intended as a definition of the limits ofthe present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention, reference isnow made to the following descriptions taken in conjunction with theaccompanying drawing.

FIG. 1 shows a schematic representation of the depth of focus.

FIG. 2 shows a collimated beam of light being refracted by a sphericallens.

FIG. 3 shows a schematic of the adaptive optics simulator used todetermine the optimized values for 4^(th) order spherical aberration anddefocus.

FIG. 4 shows a schematic of positive power adjustment mechanism; wherein(a) is a schematic representation of selective irradiation of thecentral zone of the lens in which the polymerization of the MC creates adifference in the chemical potential between the irradiated andnon-irradiated regions, (b) to reestablish equilibrium, excess MCdiffuses into the irradiated region causing swelling, and (c)irradiation of the entire lens “locks” the remaining MC and the shapechange.

FIG. 5 shows a plot of the aspheric function described in Equation 1.

FIG. 6 shows cross-sectional plots of Equation 2 generated by combininga power neutral profile with weighted amounts (β=0 to 0.57) of theaspheric profile.

FIG. 7 shows a plot of induced 4^(th) and 6^(th) order sphericalaberration as a function of increasing β value. The measurement aperturewas 4 mm and none of these LALs received any type of prior adjustment,

FIG. 8 shows a plot of induced 4^(th) and 6^(th) order sphericalaberration as a function of increasing β value for LALs receiving ahyperopic, myopic, and no prior adjustment. The measurement aperture forboth the 4^(th) and 6^(th) order spherical aberration was 4 mm.

FIG. 9 shows the monocular visual acuity data for eyes receiving aninitial refractive adjustment followed by an aspheric treatment (n=32)versus those eyes treated only for distance emmetropia (n=12).

FIG. 10 shows the segregation of the monocular visual acuity data intohigh (n=9) and low (n=23) induced spherical aberration values. Forcomparison, those eyes (n=12) adjusted for distance emmetropia are alsoshown.

FIG. 11 shows a comparison of the monocular and the binocular visualacuities for a series of patients that were corrected for distanceemmetropia in one eye and received an aspheric treatment in their felloweye. The amount of induced asphericity ranged from −0.04 μm to −0.10 μm,referenced to a 4 mm pupil.

FIG. 12 shows a comparison of the monocular and binocular visualacuities for a series of patients that were corrected for distanceemmetropia in one eye and received an aspheric treatment in their felloweye. The amount of induced asphericity ranged from −0.11 μm to −0.23 μm,referenced to a 4 mm pupil.

FIGS. 13A-D illustrate a Light Adjustable Lens with position-dependentoptical power and shifted axes, and stages of an illumination of theLight Adjustable Lens.

FIGS. 14A-B illustrate a Light Adjustable Lens with position-dependentoptical power and shifted axes.

FIGS. 15A-C illustrate a position dependent optical power in a LAL.

FIG. 16 illustrates a Light Adjustable Lens with position-dependentoptical power.

FIGS. 17A-B illustrate the visual acuity of presbyopic eyes, withimplanted EDOF or CNA LALs.

FIG. 18 illustrates the visual acuity of presbyopic eyes, with implantedEDOF+CNA LALs.

FIG. 19 illustrates a Light Adjustable Lens with a peripheral opticalpower of differently-curved radial dependence compared to FIG. 1.

FIGS. 20A-C illustrate Light Adjustable Lenses with an average centraloptical power less than an average peripheral optical power, withvarious radial dependence curvatures.

FIGS. 21A-B illustrate a LAL with a mid-range vision region.

FIG. 22 illustrates a LAL with a light-adjusted region, with a shiftedadjustment axis.

FIG. 23 illustrates the position dependent optical power of a LAL.

FIG. 24 illustrates a method of adjusting the LAL.

FIGS. 25A-B illustrate applying the first illumination and the secondillumination to the LAL within the method.

FIG. 26 illustrates applying a third illumination to the LAL.

FIGS. 27A-B illustrate applying the second and third illumination to theLAL.

FIG. 28 illustrates a method of adjusting the LAL with a pre-molded LAL.

FIG. 29 illustrates a generalized method of adjusting the LAL.

FIG. 30 illustrates a method of adjusting the LAL.

DETAILED DESCRIPTION

As used herein the specification, “a” or “an” may mean one or more. Asused herein in the claim(s), when used in conjunction with the word“comprising”, the words “a” or “an” may mean one or more than one. Asused herein “another” may mean at least a second or more. Furthermore,as used herein, the terms “comprise,” “have” and “include” areopen-ended linking verbs. Any forms or tenses of one or more of theseverbs, such as “comprises,” “comprising,” “has,” “having,” “includes”and “including,” are also open-ended. For example, any method that“comprises,” “has” or “includes” one or more steps is not limited topossessing only those one or more steps and also covers other unlistedsteps.

Throughout this application, the term “about” is used to indicate that avalue includes the inherent variation of error for the device, themethod being employed to determine the value, or the variation thatexists among the experimental test articles.

Chemical Group Definitions

When used in the context of a chemical group, “hydrogen” means —H;“hydroxy” means —OH; “oxo” means ═O; “halo” means independently —F, —Cl,—Br or —I; “amino” means —NH₂ (see below for definitions of groupscontaining the term amino, e.g., alkylamino); “hydroxyamino” means—NHOH; “nitro” means —NO₂; imino means ═NH (see below for definitions ofgroups containing the term imino, e.g., alkylimino); “cyano” means —CN;“isocyanate” means —N═C═O; “azido” means —N₃; in a monovalent context“phosphate” means —OP(O)(OH)₂ or a deprotonated form thereof; in adivalent context “phosphate” means —OP(O)(OH)O— or a deprotonated formthereof, “mercapto” means —SH; and “thio” means ═S

In the context of chemical formulas, the symbol “-” means a single bond,“═” means a double bond, and “≡” means triple bond. The symbol “----”represents an optional bond, which if present is either single ordouble. The symbol “

” represents a single bond or a double bond. Thus, for example, thestructure

includes the structures

As will be understood by a person of skill in the art, no one such ringatom forms part of more than one double bond. The symbol “

”, when drawn perpendicularly across a bond indicates a point ofattachment of the group. It is noted that the point of attachment istypically only identified in this manner for larger groups in order toassist the reader in rapidly and unambiguously identifying a point ofattachment. The symbol “

” means a single bond where the group attached to the thick end of thewedge is “out of the page.” The symbol “

” means a single bond where the group attached to the thick end of thewedge is “into the page”. The symbol “

” means a single bond where the conformation (e.g., either R or S) orthe geometry is undefined (e.g., either E or Z).

Any undefined valency on an atom of a structure shown in thisapplication implicitly represents a hydrogen atom bonded to the atom.When a group “R” is depicted as a “floating group” on a ring system, forexample, in the formula:

then R may replace any hydrogen atom attached to any of the ring atoms,including a depicted, implied, or expressly defined hydrogen, so long asa stable structure is formed. When a group “R” is depicted as a“floating group” on a fused ring system, as for example in the formula:

then R may replace any hydrogen attached to any of the ring atoms ofeither of the fused rings unless specified otherwise. Replaceablehydrogens include depicted hydrogens (e.g., the hydrogen attached to thenitrogen in the formula above), implied hydrogens (e.g., a hydrogen ofthe formula above that is not shown but understood to be present),expressly defined hydrogens, and optional hydrogens whose presencedepends on the identity of a ring atom (e.g., a hydrogen attached togroup X, when X equals —CH—), so long as a stable structure is formed.In the example depicted, R may reside on either the 5-membered or the6-membered ring of the fused ring system. In the formula above, thesubscript letter “y” immediately following the group “R” enclosed inparentheses, represents a numeric variable. Unless specified otherwise,this variable can be 0, 1, 2, or any integer greater than 2, onlylimited by the maximum number of replaceable hydrogen atoms of the ringor ring system.

For the groups and classes below, the following parenthetical subscriptsfurther define the group/class as follows. “(Cn)” defines the exactnumber (n) of carbon atoms in the group/class. “(C<n)” defines themaximum number (n) of carbon atoms that can be in the group/class, withthe minimum number as small as possible for the group in question, e.g.,it is understood that the minimum number of carbon atoms in the group“alkenyl_(C≤8))” or the class “alkene_(C≤8))” is two. For example,“alkoxy_((C≤10))>” designates those alkoxy groups having from 1 to 10carbon atoms (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any rangederivable therein (e.g., 3 to 10 carbon atoms). (Cn-n′) defines both theminimum (n) and maximum number (n′) of carbon atoms in the group.Similarly, “alkyl_((C2-10))” designates those alkyl groups having from 2to 10 carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any rangederivable therein (e.g., 3 to 10 carbon atoms)).

The term “saturated” as used herein means the compound or group somodified has no carbon-carbon double and no carbon-carbon triple bonds,except as noted below. The term does not preclude carbon-heteroatommultiple bonds, for example a carbon oxygen double bond or a carbonnitrogen double bond. Moreover, it does not preclude a carbon-carbondouble bond that may occur as part of keto-enol tautomerism orimine/enamine tautomerism.

The term “aliphatic” when used without the “substituted” modifiersignifies that the compound/group so modified is an acyclic or cyclic,but non-aromatic hydrocarbon compound or group. In aliphaticcompounds/groups, the carbon atoms can be joined together in straightchains, branched chains, or non-aromatic rings (alicyclic). Aliphaticcompounds/groups can be saturated, that is joined by single bonds(alkanes/alkyl), or unsaturated, with one or more double bonds(alkenes/alkenyl) or with one or more triple bonds (alkynes/alkynyl).When the term “aliphatic” is used without the “substituted” modifieronly carbon and hydrogen atoms are present. When the term is used withthe “substituted” modifier one or more hydrogen atom has beenindependently replaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H,—CO₂CH, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂,—OC(O)CH₃, or —S(O)₂NH₂.

The term “alkyl” when used without the “substituted” modifier refers toa monovalent saturated aliphatic group with a carbon atom as the pointof attachment, a linear or branched, cyclo, cyclic or acyclic structure,and no atoms other than carbon and hydrogen. Thus, as used hereincycloalkyl is a subset of alkyl. The groups —CH; (Me), —CH₂CH₃ (Et),—CH₂CH₂CH (n-Pr), —CH(CH₃)₂ (iso-Pr), —CH(CH₂)₂ (cyclopropyl),—CH₂CH₂CH₂CH₃ (n-Bu), —CH(CH₃)CH₂CH₃ (see-butyl), —CH₂CH(CH₃)₂(iso-butyl), —C(CH₃)₃ (tert-butyl), —CH₂C(CH₃). (neo-pentyl),cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexylmethyl arenon-limiting examples of alkyl groups. The term “alkanediyl” when usedwithout the “substituted” modifier refers to a divalent saturatedaliphatic group, with one or two saturated carbon atom(s) as thepoint(s) of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, no carbon-carbon double or triple bonds, and no atoms otherthan carbon and hydrogen. The groups, —CH₂— (methylene), —CH₂CH₂—,—CH₂C(CH₃)₂CH₂—, —CH₂CH₂CH₂—, and

are non-limiting examples of alkanediyl groups. The term “alkylidene”when used without the “substituted” modifier refers to the divalentgroup ═CRR′ in which R and R′ are independently hydrogen, alkyl, or Rand R′ are taken together to represent an alkanediyl having at least twocarbon atoms. Non-limiting examples of alkylidene groups include: ═CH₂,═CH(CH₂CH₃), and ═C(CH₃)₂. When any of these terms is used with the“substituted” modifier one or more hydrogen atom has been independentlyreplaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH,—OCHI, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.The following groups are non-limiting examples of substituted alkylgroups: —CH₂OH, —CH₂Cl, —CF₃, —CH₂CN, —CH₂C(O)OH, —CH₂C(O)OCH₃,—CH₂C(O)NH₂, —CH₂C(O)CH₃, —CH₂OCH₃, —CH₂OC(O)CH₃, —CH₂NH₂, —CH₂N(CH₃)₂,and —CH₂CH₂Cl. The term “haloalkyl” is a subset of substituted alkyl, inwhich one or more hydrogen has been substituted with a halo group and noother atoms aside from carbon, hydrogen and halogen are present. Thegroup, —CH₂Cl is a non-limiting examples of a haloalkyl. An “alkane”refers to the compound H—R, wherein R is alkyl. The term “fluoroalkyl”is a subset of substituted alkyl, in which one or more hydrogen has beensubstituted with a fluoro group and no other atoms aside from carbon,hydrogen and fluorine are present. The groups, —CH₂F, —CF₃, and —CH₂CF₃are non-limiting examples of fluoroalkyl groups. An “alkane” refers tothe compound H—R, wherein R is alkyl.

The term “alkenyl” when used without the “substituted” modifier refersto an monovalent unsaturated aliphatic group with a carbon atom as thepoint of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, at least one nonaromatic carbon-carbon double bond, nocarbon-carbon triple bonds, and no atoms other than carbon and hydrogen.Non-limiting examples of alkenyl groups include: —CH═CH (vinyl),—CH═CHCH₃, —CH═CHCH₂CH₃, —CH₂CH═CH₂ (allyl), —CH₂CH═CHCH₃, and—CH═CH—C₆H₅. The term “alkenediyl” when used without the “substituted”modifier refers to a divalent unsaturated aliphatic group, with twocarbon atoms as points of attachment, a linear or branched, cyclo,cyclic or acyclic structure, at least one nonaromatic carbon-carbondouble bond, no carbon-carbon triple bonds, and no atoms other thancarbon and hydrogen.

The groups, —CH═CH—, —CH═C(CH₃)CH₂—, —CH═CHCH₂—, and, are non-limitingexamples of alkenediyl groups. When these terms are used with the“substituted” modifier one or more hydrogen atom has been independentlyreplaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H, —CO₂CHI, —CN, —SH,—OCH₃, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH, or —S(O)₂NH₂.The groups, —CH═CHF, —CH═CHCl and —CH═CHBr, are non-limiting examples ofsubstituted alkenyl groups. An “alkene” refers to the compound H—R,wherein R is alkenyl.

The term “alkynyl” when used without the “substituted” modifier refersto an monovalent unsaturated aliphatic group with a carbon atom as thepoint of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, at least one carbon-carbon triple bond, and no atoms otherthan carbon and hydrogen. As used herein, the term alkynyl does notpreclude the presence of one or more non-aromatic carbon-carbon doublebonds. The groups, —C≡CH, —C≡CCH₃, and —CH₂CCCH₃, are non-limitingexamples of alkynyl groups. The term “alkynediyl” when used without the“substituted” modifier refers to a divalent unsaturated aliphatic group,with two carbon atoms as points of attachment, a linear or branched,cyclo, cyclic or acyclic structure, at least one carbon-carbon triplebond, and no atoms other than carbon and hydrogen. When these terms areused with the “substituted” modifier one or more hydrogen atom has beenindependently replaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H,—CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂,—OC(O)CH₃, or —S(O)₂NH₂. An “alkyne” refers to the compound H—R, whereinR is alkynyl.

The term “aryl” when used without the “substituted” modifier refers to amonovalent unsaturated aromatic group with an aromatic carbon atom asthe point of attachment, said carbon atom forming part of a one or moresix-membered aromatic ring structure, wherein the ring atoms are allcarbon, and wherein the group consists of no atoms other than carbon andhydrogen. If more than one ring is present, the rings may be fused orunfused. As used herein, the term does not preclude the presence of oneor more alkyl group (carbon number limitation permitting) attached tothe first aromatic ring or any additional aromatic ring present.Non-limiting examples of aryl groups include phenyl (Ph), methylphenyl,(dimethyl)phenyl, —C₆H₄CH₂CH₃ (ethylphenyl), naphthyl, and themonovalent group derived from biphenyl. The term “arenediyl” when usedwithout the “substituted” modifier refers to a divalent aromatic group,with two aromatic carbon atoms as points of attachment, said carbonatoms forming part of one or more six-membered aromatic ringstructure(s) wherein the ring atoms are all carbon, and wherein themonovalent group consists of no atoms other than carbon and hydrogen. Asused herein, the term does not preclude the presence of one or morealkyl group (carbon number limitation permitting) attached to the firstaromatic ring or any additional aromatic ring present. If more than onering is present, the rings may be fused or unfused. Non-limitingexamples of arenediyl groups include:

When these terms are used with the “substituted” modifier one or morehydrogen atom has been independently replaced by —OH, —F, —Cl, —Br, —,—NH, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂. An “arene” refers to thecompound H—R, wherein R is aryl.

The term “aralkyl” when used without the “substituted” modifier refersto the monovalent group -alkanediyl-aryl, in which the terms alkanediyland aryl are each used in a manner consistent with the definitionsprovided above, Non-limiting examples of aralkyls are: phenylmethyl(benzyl, Bn) and 2-phenyl-ethyl. When the term is used with the“substituted” modifier one or more hydrogen atom from the alkanediyland/or the aryl has been independently replaced by —OH, —F, —Cl, —Br,—I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂. Non-limiting examples ofsubstituted aralkyls are: (3-chlorophenyl)-methyl, and2-chloro-2-phenyl-eth-1-yl.

The term “heteroaryl” when used without the “substituted” modifierrefers to a monovalent aromatic group with an aromatic carbon atom ornitrogen atom as the point of attachment, said carbon atom or nitrogenatom forming part of an aromatic ring structure wherein at least one ofthe ring atoms is nitrogen, oxygen or sulfur, and wherein the groupconsists of no atoms other than carbon, hydrogen, aromatic nitrogen,aromatic oxygen and aromatic sulfur. As used herein, the term does notpreclude the presence of one or more alkyl group (carbon numberlimitation permitting) attached to the aromatic ring or any additionalaromatic ring present. Non-limiting examples of heteroaryl groupsinclude furanyl, imidazolyl, indolyl, indazolyl (Im), methylpyridyl,oxazolyl, pyridyl, pyrrolyl, pyrimidyl, pyrazinyl, quinolyl, quinazolyl,quinoxalinyl, thienyl, and triazinyl. The term “heteroarenediyl” whenused without the “substituted” modifier refers to an divalent aromaticgroup, with two aromatic carbon atoms, two aromatic nitrogen atoms, orone aromatic carbon atom and one aromatic nitrogen atom as the twopoints of attachment, said atoms forming part of one or more aromaticring structure(s) wherein at least one of the ring atoms is nitrogen,oxygen or sulfur, and wherein the divalent group consists of no atomsother than carbon, hydrogen, aromatic nitrogen, aromatic oxygen andaromatic sulfur. As used herein, the term does not preclude the presenceof one or more alkyl group (carbon number limitation permitting)attached to the first aromatic ring or any additional aromatic ringpresent. If more than one ring is present, the rings may be fused orunfused.

Non-limiting examples of heteroarenediyl groups include:

When these terms are used with the “substituted” modifier one or morehydrogen atom has been independently replaced by —OH, —F, —Cl, —Br, —I,—NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

The term “acyl” when used without the “substituted” modifier refers tothe group —C(O)R, in which R is a hydrogen, alkyl, aryl, aralkyl orheteroaryl, as those terms are defined above. The groups, —CHO, —C(O)CH₃(acetyl, Ac), —C(O)CH₂CH₃, —C(O)CH₂CH₂CH₃, —C(O)CH(CH₃)₂, —C(O)CH(CH₂)₂,—C(O)C₆H₅, —C(O)C₆H₄CH₃, —C(O)CH₂C₆H₅, —C(O)(imidazolyl) arenon-limiting examples of acyl groups. A “thioacyl” is defined in ananalogous manner, except that the oxygen atom of the group —C(O)R hasbeen replaced with a sulfur atom, —C(S)R. When either of these terms areused with the “substituted” modifier one or more hydrogen atom has beenindependently replaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H,—CO₂CH₃, —CN, —SH, —OCH₃, —OCHCH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂,—OC(O)CH₃, or —S(O)₂NH₂. The groups, —C(O)CH₂CF₃, —CO₂H (carboxyl),—CO₂CH₃ (methylcarboxyi), —CO₂CH₂CH₃, —C(O)NH₂ (carbamoyl), and—CON(CH₃)₂, are non-limiting examples of substituted acyl groups.

The term “alkoxy” when used without the “substituted” modifier refers tothe group —OR, in which R is an alkyl, as that term is defined above.Non-limiting examples of alkoxy groups include: —OCH₃, —OCH₂CH₃,—OCH₂CH₂CH₃, —OCH(CH₃), —OCH(CH₂)₂, —O-cyclopentyl, and —O-cyclohexyl.The terms “alkenyloxy”, “alkynyloxy”, “aryloxy”, “aralkoxy”,“heteroaryloxy”, and “acyloxy”, when used without the “substituted”modifier, refers to groups, defined as —OR, in which R is alkenyl,alkynyl, aryl, aralkyl, heteroaryl, and acyl, respectively. Similarly,the term “alkylthio” when used without the “substituted” modifier refersto the group —SR, in which R is an alkyl, as that term is defined above.When any of these terms is used with the “substituted” modifier one ormore hydrogen atom has been independently replaced by —OH, —F, —Cl, —Br,—I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂. The term “alcohol”corresponds to an alkane, as defined above, wherein at least one of thehydrogen atoms has been replaced with a hydroxy group.

The term “alkylamino” when used without the “substituted” modifierrefers to the group —NHR, in which R is an alkyl, as that term isdefined above. Non-limiting examples of alkylamino groups include:—NHCH₃ and —NHCH₂CH. The term “dialkylamino” when used without the“substituted” modifier refers to the group —NRR′, in which R and R′ canbe the same or different alkyl groups, or R and R′ can be taken togetherto represent an alkanediyl. Non-limiting examples of dialkylamino groupsinclude. —N(CH₃)₂, —N(CH₃)(CH₂CH₃), and N-pyrrolidinyl. The terms“alkoxyamino”, “alkenylamino”, “alkynylamino”, “arylamino”,“aralkylamino”, “heteroarylamino”, and “alkylsulfonylamino” when usedwithout the “substituted” modifier, refers to groups, defined as —NHR,in which R is alkoxy, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, andalkylsulfonyl, respectively. A non-limiting example of an arylaminogroup is —NHC₆H₅. The term “amido” (acylamino), when used without the“substituted” modifier, refers to the group —NHR, in which R is acyl, asthat term is defined above. A non-limiting example of an amido group is—NHC(O)CH₃. The term “alkylimino” when used without the “substituted”modifier refers to the divalent group ═NR, in which R is an alkyl, asthat term is defined above. When any of these terms is used with the“substituted” modifier one or more hydrogen atom has been independentlyreplaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH,—OCH₃, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.The groups —NHC(O)OCH₃ and —NHC(O)NHCH, are non-limiting examples ofsubstituted amido groups.

The term “alkylphosphate” when used without the “substituted” modifierrefers to the group —OP(O)(OH)(OR), in which R is an alkyl, as that termis defined above. Non-limiting examples of alkyiphosphate groupsinclude: —OP(O)(OH)(OMe) and —OP(O)(OH)(OEt). The term“dialkylphosphate” when used without the “substituted” modifier refersto the group —OP(O)(OR)(OR′), in which R and R′ can be the same ordifferent alkyl groups, or R and R′ can be taken together to representan alkanediyl. Non-limiting examples of dialkylphosphate groups include:—OP(O)(OMe)₂, —OP(O)(OEt)OMe) and —OP(O)(OEt)₂. When any of these termsis used with the “substituted” modifier one or more hydrogen atom hasbeen independently replaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H,—CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —N(CH₃)₂, —C(O)NH₂,—OC(O)CH₃, or —S(O)₂NH₂.

The terms “alkylsulfonyl” and “alkylsulfinyl” when used without the“substituted” modifier refers to the groups —S(O)₂R and —S(O)R,respectively, in which R is an alkyl, as that term is defined above. Theterms “alkenylsulfonyl”, “alkynylsulfonyl”, “arylsulfonyl”,“aralkylsulfonyl”, and “heteroarylsulfonyl”, are defined in an analogousmanner. When any of these terms is used with the “substituted” modifierone or more hydrogen atom has been independently replaced by —OH, —F,—Cl, —Br, —I, —NH₂, —N₀₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃,—C(O)CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

The term “effective,” as that term is used in the specification and/orclaims, means adequate to accomplish a desired, expected, or intendedresult. “Effective amount,” or “Therapeutically effective amount” whenused in the context of treating a patient or subject with a stimulusmeans that the amount of the stimulus which, when administered to asubject or patient for treating a condition, is sufficient to effectsuch treatment for the condition.

As used herein, the term “patient” or “subject” refers to a livingmammalian organism, such as a human, monkey, cow, sheep, goat, dog, cat,mouse, rat, guinea pig, or transgenic species thereof. In certainembodiments, the patient or subject is a primate. Non-limiting examplesof human subjects are adults, juveniles, infants and fetuses.

As generally used herein “pharmaceutically acceptable” refers to thosecompounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues, organs, and/or bodily fluids of human beings andanimals without excessive toxicity, irritation, allergic response, orother problems or complications commensurate with a reasonablebenefit/risk ratio.

A “repeat unit” is the simplest structural entity of certain materials,for example, frameworks and/or polymers, whether organic, inorganic ormetal-organic. In the case of a polymer chain, repeat units are linkedtogether successively along the chain, like the beads of a necklace. Forexample, in polyethylene, —[—CH₂CH₂—]_(n)—, the repeat unit is —CH₂CH₂—.The subscript “n” denotes the degree of polymerization, that is, thenumber of repeat units linked together. When the value for “n” is leftundefined or where “n” is absent, it simply designates repetition of theformula within the brackets as well as the polymeric nature of thematerial. The concept of a repeat unit applies equally to where theconnectivity between the repeat units extends three dimensionally, suchas in, modified polymers, thermosetting polymers, etc.

“Treatment” or “treating” includes (1) inhibiting a disease in a subjector patient experiencing or displaying the pathology or symptomatology ofthe disease (e.g., arresting further development of the pathology and/orsymptomatology), (2) ameliorating a disease in a subject or patient thatis experiencing or displaying the pathology or symptomatology of thedisease (e.g., reversing the pathology and/or symptomatology), and/or(3) effecting any measurable decrease in a disease in a subject orpatient that is experiencing or displaying the pathology orsymptomatology of the disease.

The above definitions supersede any conflicting definition in any of thereference that is incorporated by reference herein. The fact thatcertain terms are defined, however, should not be considered asindicative that any term that is undefined is indefinite. Rather, allterms used are believed to describe the invention in terms such that oneof ordinary skill can appreciate the scope and practice the presentinvention.

Compositions of the Invention

Compositions of the present disclosure may be made using the methodsdescribed above and in Example 1 below. These methods can be furthermodified and optimized using the principles and techniques of organicchemistry and/or polymer chemistry as applied by a person skilled in theart. Such principles and techniques are taught, for example, in March'sAdvanced Organic Chemistry: Reactions, Mechanisms, and Structure (2007),and/or in R. J. Young & P. A. Lovell, Introduction to Polymers, (Chapman& Hall 1991), which are incorporated by reference herein.

Discussion of General Embodiments

From a pure optical standpoint, the depth of focus (DOF) for an opticalsystem (e.g. the eye) is simply defined as the maximum movement awayfrom the ideal image plane, which may be made without causing a seriousdeterioration of the image. According to the Rayleigh limit, there willbe no appreciable deterioration of the image, i.e., no marked changefrom the Airy pattern, provided the maximum phase difference betweendisturbances arriving at the center of the pattern, does not exceed π/2.With reference to FIG. 1, this is mathematically stated as:

${\delta \; 1} = {\pm \frac{\lambda}{8_{n\sin}^{\prime 2}\frac{U^{\prime}}{2}}}$

where AP represents a spherical wave converging to the image point B, λis the wavelength, n′ is the refractive index in the image space, U′ isthe slope of the refracted ray, and 61 is the DOF. Therefore, an opticalsystem such as the human eye will have an inherent amount of depth offocus even for a perfectly imaging system.

An additional property of optical systems that can be exploited tofurther increase the depth of focus, and therefore provide for bothdistance and near vision, is spherical aberration. In simple terms,spherical aberration is defined as the variation of focus with aperture.FIG. 2 graphically depicts a collimated beam of light being refracted bya spherical biconvex lens. Notice that the rays closest to the opticalaxis come to a focus close to the paraxial focus position. As the rayheight at the lens increases, the position of the ray's intersectionwith the optical axis moves farther and farther away from the paraxialfocus. The distance from the paraxial focus to the axial intersection ofthe ray is called longitudinal spherical aberration. The image of apoint formed by a lens with spherical aberration is usually a bright dotsurrounded by a halo of light. The effect of spherical aberration on anextended image is to soften the contrast of the image and blur itsdetails. However, it should be possible to induce a specific sphericalaberration that increases the depth of focus such that the softening ofthe focus and the image contrast is acceptable.

The presence of spherical aberration increases the depth of focus in theeye. In combination with a residual refractive error (defocus), aninduced spherical aberration can be used to provide patients with goodcontrast images both for distance and near objects. The key issue is todetermine the required values of both 4^(th) order spherical aberrationand defocus that provide good near vision without deteriorating theimage quality for distance objects. An experimental approach thatpermits determination of the optimum values of spherical aberration anddefocus is an adaptive optics visual simulator. (Fernandez et al.,2002). An example of this type of instrument is shown in FIG. 3. Thisinstrument consists of a wavefront sensor (Shack-Hartmann wavefrontsensor), a wavefront corrector (Liquid Crystal on Silicon (LCOS)), andan additional optical path to present letters, e.g., a tumbling E, tothe subjects under test. The visual acuity of several subjects wasmeasured using a similar setup as that shown in FIG. 3. The visualacuity of the subjects was measured through simulations that consistedof a number of different combinations of residual defocus and sphericalaberration measurements for letter objects placed at distances from 30cm to distance emmetropia. The results of these simulations indicatethat the optimum values of negative spherical aberration and defocus tomaintain good vision between 40 cm and distance emmetropia are −0.125 μmof 4^(th) order spherical aberration in combination with −1.0 D ofdefocus.

The spherical IOL of the present invention is capable ofpost-fabrication alteration of optical properties. The lens isself-contained and does not require the addition or removal of materialsto change the optical properties. Instead, the optical properties of thelens are altered by exposing a portion or portions of the lens to anexternal stimulus which induces polymerization of a MC within the lens.The polymerization of the MC, in turn, causes the change in opticalproperties.

In some examples, the optical element of the invention has dispersedwithin it a MC. The MC is capable of diffusion within the lens; can bereadily polymerized by exposure to a suitable external stimulus; and iscompatible with the materials used to make the first polymer matrix ofthe lens.

The method for providing an aspheric lens begins with the formation ofthe first polymer matrix. After the first polymer matrix is formed, thesecond polymer matrix is formed by exposing the first polymer matrix,which further comprises the MC, to an external stimulus. During thissecond polymerization, several changes occur within the optical element.The first change is the formation of a second polymer matrix comprisingpolymerized MC. The formation of the second polymer network can causechanges in the optical properties of the element, namely the refractiveindex. In addition, when the MC polymerizes, a difference in thechemical potential between the polymerized and unpolymerized region isinduced. This in turn causes the unpolymerized MC to diffuse within theelement, which reestablishes thermodynamic equilibrium of the opticalelement. If the optical element possesses sufficient elasticity, thismigration of MC can cause swelling of the element in the area exposed tothe stimulus. This, in turn, changes the shape of the element, causingchanges in the optical properties. Whether the radius of curvature ofthe element and/or the refractive index of the element change dependsupon (1) the nature of the optical element, (2) the MC incorporated intothe element, (3) the duration that the element is exposed to thestimulus, and (4) the spatial intensity profile of the stimulus. Aschematic depicting the process for increasing the power of the lens isdisplayed in FIG. 4.

The optical element is typically made of a first polymer matrix.Illustrative examples of a suitable first polymer matrix include: (1)polyacrylates such as polyalkyl acrylates and polyhydroxyalkylacrylates; (2) polymethacrylates such as polymethyl methacrylate(“PMMA”), polyhydroxyethyl methacrylate (“PHEMA”), and polyhydroxypropylmethacrylate (“HPMA”); (3) polyvinyls such as polystyrene andpolyvinylpyrrolidone (“PNVP”); (4) polysiloxanes such aspolydimethylsiloxane; polyphosphazenes, and/or (5) copolymers thereof.U.S. Pat. No. 4,260,725 and patents and references cited therein (whichare all incorporated herein by reference) provide more specific examplesof suitable polymers that may be used to form the first polymer matrix.

In preferred embodiments, where flexibility is desired, the firstpolymer matrix generally possesses a relatively low glass transitiontemperature (“T”) such that the resulting IOL tends to exhibitfluid-like and/or elastomeric behavior, and is typically formed bycross-linking one or more polymeric starting materials wherein eachpolymeric starting material includes at least one cross-linkable group.In the case of an intraocular lens, the T_(g) should be less than 25° C.This allows the lens to be folded, facilitating implantation.

The crosslinking reaction of the polymeric starting material isaccomplished via a hydrosilylation reaction. The general scheme for thehydrosilylation reaction is shown below.

During this crosslinking step, a high molecular weight long vinyl-cappedsilicone polymer and multi-functional vinyl-capped silicone resin arecrosslinked using multifunctional hydrosilane crosslinkers. Thiscrosslinking step forms the first polymer matrix in the presence of MCand photoinitiator.

In some embodiments, the high molecular weight, long vinyl-cappedsilicone polymer has the following formula.

In some examples, m represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, m represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; L and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; L and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some embodiments, multi-functional vinyl-capped silicone resin hasthe following formula.

In some examples, x represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, x represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, y represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, y represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some embodiments, multi-functional hydrosilane crosslinker has thefollowing formula.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

Illustrative examples of suitable cross-linkable groups include but arenot limited to vinyl, hydride, acetoxy, alkoxy, amino, anhydride,aryloxy, carboxy, enoxy, epoxy, halide, isocyano, olefinic, and oxine.In more preferred embodiments, the polymeric starting material includesterminal monomers (also referred to as endcaps) that are either the sameor different from the one or more monomers that comprise the polymericstarting material but include at least one cross-linkable group. Inother words, the terminal monomers begin and end the polymeric startingmaterial and include at least one cross-linkable group as part of itsstructure. Although it is not necessary for the practice of the presentinvention, the mechanism for cross-linking the polymeric startingmaterial preferably is different than the mechanism for thestimulus-induced polymerization of the components that comprise therefraction modulating composition. For example, if the refractionmodulating composition is polymerized by photoinduced polymerization,then it is preferred that the polymeric starting materials havecross-linkable groups that are polymerized by any mechanism other thanphotoinduced polymerization.

An especially preferred class of polymeric starting materials for theformation of the first polymer matrix is polysiloxanes (also known as“silicones”) endcapped with a terminal monomer which includes across-linkable group selected from the group consisting of vinyl,acetoxy, amino, alkoxy, halide, hydroxy, and mercapto. Because siliconeIOLs tend to be flexible and foldable, generally smaller incisions maybe used during the IOL implantation procedure. An example of anespecially preferred polymeric starting materials are vinyl endcappeddimethylsiloxane diphenylsiloxane copolymer, silicone resin, andsilicone hydride crosslinker that are crosslinked via an additionpolymerization by platinum catalyst to form the silicone matrix (see theabove reaction scheme). Other such examples may be found in U.S. Pat.Nos. 5,236,970; 5,376,694; 5,278,258; 5,444,106; and, others similar tothe described formulations. U.S. Pat. Nos. 5,236,970; 5,376,694;5,278,258; and 5,444,106 are incorporated herein by reference in theirentirety.

The MC that is used in fabricating IOLs is as described above exceptthat it has the additional requirement of biocompatibility. The MC iscapable of stimulus-induced polymerization and may be a single componentor multiple components so long as: (1) it is compatible with theformation of the first polymer matrix; (2) it remains capable ofstimulus-induced polymerization after the formation of the first polymermatrix; and (3) it is freely diffusible within the first polymer matrix.

In general, the same type of monomers that are used to form the firstpolymer matrix may be used as components of the refraction modulatingcomposition. However, because of the requirement that the MC macromermust be diffusible within the first polymer matrix, the MC macromersgenerally tend to be smaller (i.e., have lower molecular weights) thanthe starting polymeric materials used to form the first polymer matrix.In addition to the one or more monomers, the MC may include othercomponents such as initiators and sensitizers that facilitate theformation of the second polymer network.

In preferred embodiments, the stimulus-induced polymerization isphotopolymerization. In other words, the one or more monomers ormacromers that comprise the refraction modulating composition eachpreferably includes at least one group that is capable ofphotopolymerization. Illustrative examples of such photopolymerizablegroups include but are not limited to acrylate, allyloxy, cinnamoyl,methacrylate, stibenyl, and vinyl. In more preferred embodiments, therefraction modulating composition includes a photoinitiator (anycompound used to generate free radicals) either alone or in the presenceof a sensitizer. Examples of suitable photoinitiators includeacetophenones (e.g., substituted haloacetophenones, anddiethoxyacetophenone); 2,4-dichloromethyl-1,3,5-trazines; benzoin methylether; and o-benzoyl oximino ketone. Examples of suitable sensitizersinclude p-(dialkyiamino)aryl aldehyde; N-alkylindolylidene; andbis[p-(dialkylamino)benzylidene] ketone.

Because of the preference for flexible and foldable IOLs, an especiallypreferred class of MC monomers is polysiloxanes endcapped with aterminal siloxane moiety that includes a photopolymerizable group.Non-limiting examples of a suitable photopolymerizable group include,but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate,stibenyl, and vinyl. An illustrative representation of such a monomeris:

X—Y—X′

wherein Y is a siloxane which may be a monomer, a homopolymer or acopolymer formed from any number of siloxane units, and X and X′ may bethe same or different and are each independently a terminal siloxanemoiety that includes a photopolymerizable group. Non-limiting examplesof a suitable photopolymerizable group include, but are not limited toacrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl. Anillustrative example of Y includes:

wherein m and n are independently each an integer; and, R¹, R², R³, andR⁴ are independently each hydrogen, alkyl (substituted, primary,secondary, tertiary, cycloalkyl), aryl, or heteroaryl. In preferredembodiments, R¹, R², R³, and R⁴ are independently C₁-C₁₀ alkyl orphenyl. Because MC monomers with a relatively high aryl content havebeen found to produce larger changes in the refractive index of theinventive lens, it is generally preferred that at least one of R¹, R²,R³, and R⁴ is an aryl, particularly phenyl. In more preferredembodiments, R¹, R², and R¹ are the same and are methyl, ethyl or propylwith the proviso that R⁴ is phenyl.

In some examples, m represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, m represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

Illustrative examples of X and X¹ (or X¹ and X depending on how the MCpolymer is depicted) are:

respectively wherein: R⁵ and R⁶ are independently each hydrogen, alkyl,aryl, or heteroaryl; and Z is a photopolymerizable group.

In preferred embodiments R⁵ and R⁶ are independently each C₁-C₁₀ alkylor phenyl and Z is a photopolymerizable group that includes a moietyselected from the group consisting of acrylate, allyloxy, cinnamoyl,methacrylate, stibenyl, and vinyl. In more preferred embodiments, R⁵ andR⁶ are methyl, ethyl, or propyl and Z is a photopolymerizable group thatincludes an acrylate or methacrylate moiety.

In some embodiments, a MC macromer has the following formula:

wherein X and X¹ are the same as defined above, and wherein R¹, R², R³,and R⁴ are the same as defined above. In some examples, m represents aninteger having a value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500;1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and500 or any range found within any of the aforementioned ranges. In someexamples, m represents an integer having an average value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In general, a suitable modifying composition consists of a lowermolecular weight polydimethyl-siloxane macromer containing polymerizablemethacrylate functional end groups and a bezoin photoinitiator. In someembodiments, a suitable modifying composition has the following formula.

The above structure is a polydimethyl siloxane end-capped withphotopolymerizable methacrylate functional groups. In some examples, xrepresents an integer having a value between 1 and 10,000; 1 and 9,500;1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000;1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and1,000; 1 and 500 or any range found within any of the aforementionedranges. In some examples, x represents an integer having an averagevalue between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500;1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 or any rangefound within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some embodiments, a suitable modifying composition has the followingformula.

The above modifying composition has a structure comprising apolydimethyl siloxane end-capped with benzoin photoinitiator. In someexamples, x represents an integer having a value between 1 and 10,000; 1and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500;1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, x represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

Additional illustrative examples of such MC monomers includedimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyldimethylsilane group (see below);

In some examples, m represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, m represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

Another illustrative examples of such MC monomers includesdimethylsiloxane-methylphenylsiloxane copolymer endcapped with amethacryloxypropyl dimethylsilane group (see below);

In some examples, m represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, m represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

A preferred modifying composition is the dimethylsiloxane macromerendcapped with a methacryloxypropyldimethylsilane group (see below).

In some examples, x represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, x represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

Although any suitable method may be used, a ring-opening reaction of oneor more cyclic siloxanes in the presence of triflic acid has been foundto be a particularly efficient method of making a class of MC monomers.Briefly, the method comprises contacting a cyclic siloxane with acompound of the formula:

in the presence of triflic acid wherein R¹ and R⁶ are independently eachhydrogen, alkyl, aryl, or heteroaryl; and Z is a photopolymerizablegroup. The cyclic siloxane may be a cyclic siloxane monomer,homopolymer, or copolymer. Alternatively, more than one cyclic siloxanemay be used. For example, a cyclic dimethylsiloxane tetrameter and acyclic methyl-phenylsiloxane trimer are contacted withbis-methacryloxypropyltetramethyldisiloxane in the presence of triflicacid to form a dimethyl-siloxane methyl-phenylsiloxane copolymer that isendcapped with a methacryloxylpropyl-dimethylsilane group, an especiallypreferred MC monomer, such as the MC monomer shown below.

In some examples, x represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, x represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; L and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In addition to the silicone-based MCs described above, acrylate-based MCcan also be used in the practice of the invention. The acrylate-basedmacromers of the invention have the general structure wherein X and X′may be the same or different and/or are each independently a terminalsiloxane moiety that includes a photopolymerizable group. Non-limitingexamples of a suitable photopolymerizable group include, but are notlimited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, andvinyl

X-A_(n)-Q-A_(n)-X¹

or

X-A_(n)-A¹ _(m)-Q-A¹ _(m)-A_(n)-X¹

wherein Q is an acrylate moiety capable of acting as an initiator forAtom Transfer Radical Polymerization (“ATRP”), A and A¹ have the generalstructure:

wherein R¹ is selected from the group comprising alkyls, halogenatedalkyls, aryls and halogenated aryls and X and X¹ are groups containingphotopolymerizable moieties and m and n are integers. In some examples,m represents an integer having a value between 1 and 10,000; 1 and9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000;1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500;1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, m represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In some examples, n represents an integer having a value between 1 and10,000; 1 and 9,500; 1 and 9,000; 1 and 8,500; 1 and 8,000; 1 and 7,500;1 and 7,000; 1 and 6,500; 1 and 6,000; 1 and 5,500; 1 and 5,000; 1 and4,500; 1 and 4,000; 1 and 3,500; 1 and 3,000; 1 and 2,500; 1 and 2,000;1 and 1,500; 1 and 1,000; 1 and 500 or any range found within any of theaforementioned ranges. In some examples, n represents an integer havingan average value between 1 and 10,000; 1 and 9,500; 1 and 9,000; 1 and8,500; 1 and 8,000; 1 and 7,500; 1 and 7,000; 1 and 6,500; 1 and 6,000;1 and 5,500; 1 and 5,000; 1 and 4,500; 1 and 4,000; 1 and 3,500; 1 and3,000; 1 and 2,500; 1 and 2,000; 1 and 1,500; 1 and 1,000; 1 and 500 orany range found within any of the aforementioned ranges.

In one embodiment the acrylate based MC macromer has the formula:

wherein R² is alkyl or halogenated alkyl; R³ is alkyl, halogenatedalkyl, aryl or halogenated aryls; R⁴ is alkyl, halogenated alkyl, arylor halogenated aryl; and, with the proviso that R³ and R⁴ are different.In some embodiments, the value of n is between 1 and 200; 1 and 190; 1and 180; 1 and 170; 1 and 160; 1 and 150; 1 and 140; 1 and 130; 1 and120; 1 and 10; 1 and 100; 1 and 90; 1 and 80; 1 and 70; 1 and 60; 1 and50; 1 and 40; 1 and 30; 1 and 20; 1 and 10; or any range in between. Forexample, when the value of n is between 1 and 200, this alsocontemplates a value of n between 17 and 24. In some embodiments thevalue of m is between 1 and 200; 1 and 190; 1 and 180; 1 and 170; 1 and160; 1 and 150; 1 and 140; 1 and 130; 1 and 120; 1 and 110; 1 and 100; 1and 90; 1 and 80; 1 and 70; 1 and 60; 1 and 50; 1 and 40; 1 and 30; 1and 20; 1 and 10; or any range in between. For example, when the valueof m is between 1 and 200, this also contemplates a value of m between17 and 24.

After the optical element is formed, it is then positioned in the areawhere the optical properties are to be modified. For an intraocularlens, this means implantation into the eye using known procedures. Oncethe element is in place and is allowed to adjust to its environment, itis then possible to modify the optical properties of the element throughexposure to an external stimulus.

The nature of the external stimulus can vary but it must be capable ofreducing polymerization of the MC without adversely affecting theproperties of the optical element. Typical external stimuli that can beused in practice of the invention include heat and light, with lightpreferred. In the case of intraocular lenses, ultraviolet or infraredradiation is preferred with ultraviolet light most preferred.

When the element is exposed to the external stimulus, the MCpolymerization forms a second polymer matrix, interspersed within thefirst polymer matrix. When the polymerization is localized or when onlya portion of the MC is polymerized, there is a difference in thechemical potential between the reacted and unreacted regions of thelens. The MC then migrates within the element to reestablish thethermodynamic equilibrium within the optical element.

The formation of the second polymer matrix and the re-distribution ofthe MC can each affect the optical properties of the element. Forexample, the formation of the second polymer matrix can cause changes inthe refractive index of the element. The migration of the modifyingcompound can alter the overall shape of the element, further affectingthe optical properties by changing the radii of curvatures of theoptical element.

It is possible to expose the optical element to a spatially definedirradiance profile to create a lens with different optical properties.In one embodiment, it is possible to create an intraocular lens that canbe converted into an aspheric lens after implantation. This isaccomplished by exposing the lens to a mathematically defined spatialirradiance profile. An example of the type of profiles that can be usedto induce asphericity in the lens are of the form

Asph(φ=Aρ ⁴ −Bρ ²+1  (1)

where A and B are coefficients and ρ is a radial coordinate. Anormalized plot of this function, where A=B=4, is displayed in FIG. 5.

Another approach is to linearly combine weighted amounts of the profile(Asph) displayed in equation 1 with spatial irradiance profiles that arecurrently used to correct for spherical refractive errors andspherocylindrical refractive errors as well as with Power NeutralProfiles, i.e., profiles that neither add or subtract refractive powerfrom the LAL. This approach has the dual benefits of correcting thelower aberrations, e.g. sphere and cylinder, along with imparting therequisite amount of induced asphericity to provide increased depth offocus. This can be described mathematically as follows:

Profile(ρ)=SCN(ρ)+βAsph(ρ)  (2)

where SCN(ρ) refers to either a spherical, spherocylindrical or powerneutral spatial irradiance profile, Asph(ρ) is the same as in equation1, and β is a weighting factor that can range from 0 to 1. As an exampleof this approach, consider the cross-sectional profiles shown in FIG. 6.These plots were generated by combining weighted amounts of the profilerepresented by equation 1 with a power neutral profile.

By way of a reaction sequence, the following example shows how theformation of the second polymer matrix and the re-distribution of the MCis accomplished. In the example provided below, the MC having theformula:

is exposed to UV light, thereby creating a radical species. This processis represented schematically in the reaction scheme below.

After exposing the MC to UV light, the resulting radical species arefree to react with the first polymer matrix. In the example, below thefirst polymer matrix was formed using a polymer having the followingstructure:

The radical species generated by exposing the MC to UV light then reactswith the first polymer matrix according to the reaction scheme below:

The reaction scheme for photopolymerization of photo-reactive MC in thepresence of the first polymer lens matrix is the same for the adjustmentand lock-in procedures. The difference between the adjustment procedureand lock-in procedure is the spatial irradiance profiles applied to eachprocedure.

EXAMPLES

The following examples are included to demonstrate preferred embodimentsof the invention. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques discovered by the inventor to function well in the practiceof the invention, and thus can be considered to constitute preferredmodes for its practice. However, those of skill in the art should, inlight of the present disclosure, appreciate that many changes can bemade in the specific embodiments which are disclosed and still obtain alike or similar result without departing from the spirit and scope ofthe invention.

Example 1

A series of light adjustable lenses containing a silicone-based MC wereprepared using standard molding techniques known to those skilled in theart. The lens had a first polymer matrix prepared from a siliconehydride crosslinked vinyl endcapped diphenylsiloxane dimethylsiloxane.The first polymer matrix comprised about 70 weight % of the lens. Thelens also comprised about 30 weight % of a MC (methacrylate endcappedpolydimethylsiloxane), 1 weight % (based on MC) of a photoinitiator(benzoin-tetrasiloxane-benzoin), and 0.04 weight % (based on MC) UVabsorber. The lenses had an initial nominal power of +20.0 diopters.Twelve groups, of four LALs each, were exposed to a spatial irradianceprofile defined by Equation 2 with beta values ranging from 0.05 to0.57. Table 1 summarizes the specific spatial irradiance profile,average irradiance, and time applied to each of the LAL groups. At 48hours post irradiation, the wavefronts of each of the lenses wasmeasured. The measured 4^(th) (Z12) and 6^(th) (Z24) order sphericalaberration values for each of the 12 irradiation groups were averagedtogether and plotted as a function of increasing 3 value as show in FIG.7.

TABLE 1 Summary of treatment conditions and induced spherical aberrationfor those lenses that did not receive a prior adjustment. Themeasurement aperture was 4 mm for all spherical aberration measurements.Duration Applied Power Bm Size Δ4th Order SA Δ6th Order SA Lens IDProfile (sec) (mW) (mm) ΔZ12 (μm) ΔZ24 (μm) 6699 In-vitro PN Profile +Beta = 0.05 90 4.130 5.30 0.194 0.016 6701 In-vitro PN Profile + Beta =0.05 90 4.130 5.30 0.115 0.050 6706 In-vitro PN Profile + Beta = 0.05 904.130 5.30 0.003 0.054 6708 In-vitro PN Profile + Beta = 0.05 90 4.1305.30 0.029 0.053 Average 0.085 0.043 St. Dev 0.087 0.018 189-26 In-vitroPN Profile + Beta = 0.10 90 3.820 5.30 −0.019 0.017 189-29 In-vitro PNProfile + Beta = 0.10 90 3.820 5.30 −0.024 0.017 189-31 In-vitro PNProfile + Beta = 0.10 90 3.820 5.30 −0.020 0.016 189-33 In-vitro PNProfile + Beta = 0.10 90 3.820 5.30 −0.036 0.013 Average −0.025 0.016St. Dev 0.008 0.002 189-27 In-vitro PN Profile + Beta = 0.15 90 3.6705.30 −0.056 0.013 189-30 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30−0.055 0.013 189-32 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30−0.054 0.012 189-34 In-vitro PN Profile + Beta = 0.15 90 3.670 5.30−0.060 0.010 Average −0.056 0.012 St. Dev 0.003 0.001 189-35 In-vitro PNProfile + Beta = 0.20 90 3.510 5.30 −0.088 0.018 189-38 In-vitro PNProfile + Beta = 0.20 90 3.510 5.30 −0.088 0.013 189-40 In-vitro PNProfile + Beta = 0.20 90 3.510 5.30 −0.083 0.018 189-44 In-vitro PNProfile + Beta = 0.20 90 3.510 5.30 −0.081 0.013 Average −0.085 0.015St. Dev 0.003 0.003 189-37 In-vitro PN Profile + Beta = 0.25 90 3.3605.30 −0.107 0.013 189-39 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30−0.111 0.006 189-41 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30−0.106 0.009 189-45 In-vitro PN Profile + Beta = 0.25 90 3.360 5.30−0.130 0.006 Average −0.113 0.009 St. Dev 0.011 0.003 165-3-2 In-vitroPN Profile + Beta = 0.30 90 3.210 5.30 −0.151 0.010 185-3-15 In-vitro PNProfile + Beta = 0.30 90 3.210 5.30 −0.156 0.008 188-2-18 In-vitro PNProfile + Beta = 0.30 90 3.210 5.30 −0.163 0.012 189-47 In-vitro PNProfile + Beta = 0.30 90 3.210 5.30 −0.148 0.007 Average −0.155 0.009St. Dev 0.007 0.002 185-3-11 In-vitro PN Profile + Beta = 0.35 90 3.0605.30 −0.193 0.005 188-2-16 In-vitro PN Profile + Beta = 0.35 90 3.0605.30 −0.194 0.003 189-46 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30−0.192 0.002 189-48 In-vitro PN Profile + Beta = 0.35 90 3.060 5.30−0.182 0.002 Average −0.190 0.003 St. Dev 0.006 0.002 6700 In-vitro PNProfile + Beta = 0.40 90 2.900 5.30 −0.240 0.013 6704 In-vitro PNProfile + Beta = 0.40 90 2.900 5.30 −0.241 0.011 6707 In-vitro PNProfile + Beta = 0.40 90 2.900 5.30 −0.222 0.011 6709 In-vitro PNProfile + Beta = 0.40 90 2.900 5.30 −0.224 0.017 Average −0.232 0.013St. Dev 0.010 0.003 6710 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30−0.277 0.004 6712 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 −0.2840.003 6715 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 −0.274 0.0066717 In-vitro PN Profile + Beta = 0.45 90 2.750 5.30 −0.266 −0.002Average −0.275 0.003 St. Dev 0.007 0.003 6713 In-vitro PN Profile + Beta= 0.50 90 2.600 5.30 −0.303 0.001 6716 In-vitro PN Profile + Beta = 0.5090 2.600 5.30 −0.322 −0.002 6718 In-vitro PN Profile + Beta = 0.50 902.600 5.30 −0.318 −0.009 Average −0.314 −0.003 St. Dev 0.010 0.005 6719In-vitro PN Profile + Beta = 0.55 90 2.600 5.30 −0.356 −0.009 6723In-vitro PN Profile + Beta = 0.55 90 2.600 5.30 −0.347 −0.016 6727In-vitro PN Profile + Beta = 0.55 90 2.600 5.30 −0.350 −0.011 6729In-vitro PN Profile + Beta = 0.55 90 2.600 5.30 −0.350 −0.021 Average−0.351 −0.014 St. Dev 0.004 0.006 6721 In-vitro PN Profile + Beta = 0.5790 2.600 5.30 −0.368 −0.015 6725 In-vitro PN Profile + Beta = 0.57 902.600 5.30 −0.350 −0.026 6728 In-vitro PN Profile + Beta = 0.57 90 2.6005.30 −0.359 −0.019 6730 In-vitro PN Profile + Beta = 0.57 90 2.600 5.30−0.385 −0.030 Average −0.366 −0.022 St. Dev 0.015 0.007

Inspection of the plot indicates several interesting features. The firstis the nearly linearly increase in induced 4^(th) order sphericalaberration as a function of increasing β value. The second feature isthe nearly complete absence of any 6^(th) order spherical aberrationinduction, indicating that the induced spherical aberration isessentially pure 4^(th) order spherical aberration. This is importantbecause it has been shown that the presence of 6^(th) order sphericalaberration will have the affect of nulling out any induced depth offocus produced by the induction of negative 4 order sphericalaberration. (Thibos el al., 2004) The third feature to note is the smallstandard deviation in the average, induced 4^(th) order sphericalaberration for a specific a value. This fact indicates that it ispossible to adjust the amount of asphericity in the LAL by targeted,discrete values, which will allow true customization of patients' depthof focus. And finally, as written above, the targeted amount of totalocular 4^(th) order spherical aberration for optimizing visual acuitybetween 40 cm and distance emmetropia is −0.125 μm. Inspection of thedata in Table 2 and FIG. 7 and assuming an average starting ocularspherical aberration at a 4 mm aperture of +0.10 μm, indicates that theprofile with a beta value of 0.40 would be ideal for inducing therequisite amount of negative asphericity.

The above example involved irradiating LALs that had not received aprior adjustment. However, there will be instances where it is necessaryto first adjust the spherical and/or spherocylindrical power of the LALbefore the aspheric adjustment. The LAL is a closed thermodynamicsystem, i.e. we can't add or remove particles, MC, from the lens. As aconsequence, each subsequent refractive adjustment consumes MC leavingless for subsequent adjustments. In addition, upon polymerization of MCduring adjustment, the polymerized MC forms an interpenetrating matrixwith the host matrix polymer. This action has the effect of increasingthe stiffness of the lens. Because the refractive change, i.e.spherical, spherocylindrical, aspheric, etc., of the LAL is accomplishedby a shape change, the amount of induced asphericity after an initialadjustment should be reduced for same treatment conditions as with theno prior adjustment cases summarized in FIG. 7.

To investigate this, a series of LALs were initially given either amyopic or hyperopic primary adjustment followed by an aspheric treatment48 hours post the initial, primary adjustment. FIG. 8 displays both the4^(th) and 6^(th) order spherical aberration values for LALs thatreceived either an initial hyperopic or myopic adjustment followed by anaspheric treatment with beta values ranging between 0.30 and 0.57. Forcomparison, the LALs that received the aspheric treatment as a primaryadjustment are also plotted on the same graph.

Inspection and comparison of the data for the different treatmentconditions indicate several interesting trends. The first overall themeis that, as expected, increasing the beta value, which effectivelyincreases the amount of aspheric character of the treatment beam, hasthe effect of increasing the amount of induced 4^(th) order asphericityin the LAL. This is true whether the LAL initially received a primaryadjustment or if the LAL has received no prior adjustment. The secondthing to note is that for a given beta, mediated aspheric profile, thetype of refractive adjustment preceding the aspheric treatment directlyimpacts how much 4^(th) order asphericity is induced in the lens. Forexample, consider the three different sets of LALs that were adjustedwith the β=0.57 aspheric profile after a hyperopic adjustment, a myopicadjustment, and no adjustment. Inspection of the graph indicates thatthose lenses receiving no prior adjustment displayed the largest amountof induced 4^(th) order spherical aberration, followed by the LALs thatinitially received a myopic adjustment, with the LALs after a hyperopicadjustment showing the smallest amount of induced asphericity. Thereasons for this general trend are twofold. The first, which wasdiscussed above, is due to the simple fact that the LALs that receivedno prior adjustment obviously have more starting MC and the LAL matrixis not as stiff as compared to the other two sets of LALs and thus, forthe same given aspheric dose, should show more 4^(th) order asphericityinduction. The reasons why the LALs receiving an initial myopicadjustment display greater amounts of induced 4^(th) order sphericalaberration as compared to those LALs receiving a hyperopic adjustment astheir primary adjustment, even though the magnitude of the refractivechange (−1.0 D vs +1.0 D) is the same, can be explained by the fact thatthe total energy underneath the spatial irradiance profile for the givenmyopic adjustment is less than that as compared to the hyperopicadjustment profile. Because of this fact, more macromer will be consumedduring the initial hyperopic adjustment and a stronger, interpenetratingnetwork will be formed, thus preventing more aspheric induction. Anotherimportant aspect of the data to note, is that regardless of prioradjustment, the application of the aspheric treatment does not induceany 6^(th) order spherical aberration.

Example 2

To test the ability of the aspheric adjustment profiles to induce enoughasphericity to provide patients with increased depth of focus, a seriesof subjects were implanted with the light adjustable lens after routinecataract surgery, given a prior treatment to correct for postoperativeresidual sphere and cylinder, and then given an aspheric adjustmentusing the corneal compensated versions of the profiles described inExample 1. FIG. 9 and Table 2 summarize the monocular visual acuity datafor a series of 32 eyes adjusted with aspheric profiles possessing abeta value between 0.40 and 0.57. For comparison, the averageuncorrected visual acuity values for 12 eyes implanted with a LAL andadjusted for distance emmetropia only, are displayed as well. All of theLALs received some type of primary adjustment before the application ofthe aspheric profile.

Inspection of the graph in FIG. 9 indicates several important features.The first is that, on average, from 40 cm to distance emmetropia, thepatients adjusted with an aspheric treatment profile possesseduncorrected visual acuities between 20/20 and 20/32. In fact, assummarized in Table 2, 75% of the eyes treated with the aspheric profiletreatment regimen, possess an uncorrected visual acuity of 20/32 orbetter from 40 cm to distance emmetropia. In contrast, inspection of theresults for those eyes receiving treatment to correct for residualspherical and spherocylindrical refractive errors, only, show that whilethe distance, uncorrected visual acuity results are better than theaspheric cases (83%>20/20 and 100%>20/25 or better), these eyes, asexpected, have essentially no near vision capability, i.e. 8% (1/12) seeat least 20/32 at 40 cm. Therefore, this data indicates that theapplication of the aspheric profiles to implanted LALs has the abilityto increase the depth of focus of a patients' eye.

TABLE 2 Monocular visual acuity (VA) results for those eyes receiving anaspheric treatment (n = 32). VA FAR 60 cm 40 cm Far BCVA ≥20/ 9/32 (28%)17/32 (53%) 2/32 (6%) 21/32 (65%) 20 ≥20/ 23/32 (72%) 27/32 (84%) 11/32(35%) 31/32 (97%) 25 ≥20/ 28/32 (88%) 32/32 (100%) 24/32 (75%) 32/32(100%) 32 ≥20/ 32/32 (100%) 32/32 (100%) 31/32 (97%) 32/32 (100%) 40≥20/ 32/32 (100%) 32/32 (100%) 32/32 (100%) 32/32 (100%) 60

TABLE 3 Monocular visual acuity (VA) results for those LAL eyes adjustedfor distance visual acuity only (n = 12). VA FAR 60 cm 40 cm Far BCVA≥20/ 10/12 (83%) 1/12 (8%) 0/12 (0%) 12/12 (100%) 20 ≥20/ 12/12 (100%)3/12 (25%) 0/12 (0%) 12/12 (100%) 25 ≥20/ 12/12 (100%) 8/12 (67%) 1/12(8%) 12/12 (100%) 32 ≥20/ 12/12 (100%) 12/12 (100%) 7/12 (58%) 12/12(100%) 40 ≥20/ 12/12 (100%) 12/12 (100%) 12/12 (100%) 12/12 (100%) 60

As indicated in FIG. 9, the total measured 4^(th) order sphericalaberration over a 4 mm pupil in the 32 eyes ranged from −0.04 μm to−0.23 μm. As stated above, theoretical considerations indicate that theideal amount of final 4s order spherical aberration to provide optimalvisual acuity between 40 cm and distance emmetropia is −0.125 μm. Toconsider the impact of this range of induced negative asphericity on thefinal visual acuities at different object distances, FIG. 10 segregatesthe 32 eyes into two groups: High Spherical Aberration (−0.10 μm to−0.23 μm) and Low Spherical Aberration (−0.04 μm to −0.10 μm). Asexpected, those eyes with higher amounts of induced negative sphericalaberration, on average, show better visual acuities at 40 cm (78% 7/9patients≥20/25 or J1) then those with lower spherical aberration (22%,5/23 patients a 20/25 or J1) with a slight decrease in their distancevisual acuities (56% vs 78% at 20/25). However, inspection of the VAacuity curves from 40 cm to distance emmetropia in FIG. 10, indicatethat, on average, the curve is quite flat and the majority of the eyespossess visual acuities of 20/25 or better. Comparison again with the 12eyes adjusted for distance emmetropia only, indicates that from 40 cm todistance emmetropia, the eyes that received some type of asphericinduction achieve much greater range of vision, i.e. increased depth offocus.

TABLE 4 Monocular visual acuity (VA) results for those eyes with lowamounts of final 4^(th) order spherical aberration, −0.04 to −0.10 μm (n= 23). VA FAR 60 cm 40 cm Far BCVA ≥20/20 (J1+) 7/23 (30%) 12/23 (8%)0/23 (0%) 15/23 (65%) ≥20/25 (J1) 15/23 (74%) 19/23 (83%) 5/23 (22%)22/23 (96%) ≥20/32 (J2) 20/23 (100%) 23/23 (100%) 15/23 (65%) 12/12(100%) ≥20/40 (J3) 23/23 (100%) 23/23 (100%) 23/23 (100%) 12/12 (100%)≥20/60 23/23 (100%) 23/23 (100%) 23/23 (100%) 12/12 (100%)

TABLE 5 Monocular visual acuity (VA) results for those eyes with highamounts of final 4th order spherical aberration, −0.11 to −0.23 μm (n =9). VA FAR 60 cm 40 cm Far BCVA ≥20/20 (J1+) 2/9 (22%) 4/9 (8%) 2/9(22%) 6/9 (67%) ≥20/25 (J1) 5/9 (56%) 7/9 (78%) 7/9 (78%) 8/9 (89%)≥20/32 (J2) 8/9 (89%) 8/9 (89%) 9/9 (100%) 9/9 (100%) ≥20/40 (J3) 9/9(100%) 9/9 (100%) 9/9 (100%) 9/9 (100%) ≥20/60 9/9 (100%) 9/9 (100%) 9/9(100%) 9/9 (100%)

The above discussion considered the monocular visual acuities of thetreated eyes, only. However, one approach that will optimize post LALimplantation patients' vision at all distances is to correct one of thepatients' eyes (usually the dominant eye) to distance emmetropia andthen to adjust the other eye of the patient first to distance emmetropiafollowed by application of the aspheric treatment. As an example of thisprocedure, consider the data displayed in FIG. 11 and Table 6, whichdisplays both the monocular and binocular visual acuities for a seriesof patients (n=10) that had a low (−0.04 μm to −0.10 μm) amount ofspherical aberration induced in one eye and the other eye was implantedwith a LAL and adjusted for distance emmetropia. For the distancedominant eye, the final refraction varied between piano and −0.50 D.Inspection of the monocular visual acuity results for the two eyesdisplays the same visual characteristics already discussed; namely, theeye corrected for distance emmetropia displays excellent distance visualacuity, but rather poor near vision and the aspheric eyes displayimproved depth of focus at the expense of some distance visual acuity.However, the binocular visual acuity data indicates that combining thetwo eyes provide outstanding visual acuities from 40 cm to distanceemmetropia. In fact, 100% of the patients possessed a visual acuity of20/25 or better from 40 cm to distance emmetropia.

TABLE 6 Binocular visual acuity (VA) results for those eyes with lowamounts of final 4th order spherical aberration, −0.04 to −0.10 mm intheir non-dominant eye and with their other eye adjusted for distanceemmetropia. The refraction in the dominant eye ranged from +0.25 D to−0.25 D (n = 10). VA FAR 60 cm 40 cm 30 cm ≥20/20 (J1+) 6/10 (60%) 8/10(80%) 1/10 (10%) 0/10 (0%) ≥20/25 (J1) 10/10 (100%) 10/10 (100%) 4/10(40%) 0/10 (0%) ≥20/32 (J2) 10/10 (100%) 10/10 (100%) 10/10 (100%) 3/10(30%) ≥20/40 (J3) 10/10 (100%) 10/10 (100%) 10/10 (100%) 8/10 (80%)≥20/60 10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%)

Combining this binocular approach with those eyes having high amounts ofinduced asphericity (−0.11 μm to −0.23 μm), indicates that 100% (4/4) ofthe patients possessed an uncorrected visual of 20/25 or better from 40cm to distance emmetropia.

TABLE 7 Binocular visual acuity (VA) results for those eyes with highamounts of final 4th order spherical aberration, −0.11 to −0.23 μm intheir non-dominant eye and with their other eye adjusted for distanceemmetropia. The refraction in the dominant eye ranged from +0.25 D to−0.25 D (n = 4). VA FAR 60 cm 40 cm 30 cm ≥20/20 4/4 (100%) 3/4 (75%)1/10 (10%) 0/4 (0%) (J1+) ≥20/25 (J1) 4/4 (100%) 4/4 (100%) 4/4 (100%)1/4 (25%) ≥20/32 (J2) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4 (100%) ≥20/40(J3) 4/4 (100%) 4/4 (100%) 4/4 (100%) 4/4 (100%) ≥20/60 4/4 (100%) 4/4(100%) 4/4 (100%) 4/4 (100%)

Example 3

General examples disclosed herein include an optical element composed ofmatrix polymer and a modulating composition (MC) that can be polymerizedby an external stimulus (e.g. heat, light, etc) to control the amount ofinduced asphericity.

In each of the aforementioned examples, the lens may include an opticalelement that is a lens. In additional examples, the optical element isan intraocular lens (IOL). Also, the amount of induced asphericity iscontrolled by the application of a specific spatial irradiance profile.In some examples, the amount of induced asphericity is inducedmonocularly to induce extended depth of focus.

In particular examples, the amount of induced asphericity is tailored toprovide intermediate vision (60-80 cm) or near vision (30-40 cm). Inspecific embodiments, the amount of induced asphericity can becustomized for specific individual values.

In certain embodiments, the amount of induced asphericity is inducedbinocularly to induce extended depth of focus. In particular examples,one eye is tailored for intermediate (60-80 cm) vision by the inductionof a particular value of asphericity and the other eye is corrected fordistance emmetropia. In alternate embodiments, one eye is tailored fornear vision (30-40 cm) by the induction of a particular value ofasphericity and the other eye is corrected for distance emmetropia. Infurther embodiments, both eyes are tailored for intermediate (60-80 cm)vision by the induction of particular value of asphericity. In yetanother embodiment, both eyes are tailored for near (3040 cm) vision bythe induction of particular value of asphericity. In some embodiments,one eye is tailored for intermediate (60-80 cm) vision by the inductionof negative asphericity and the other eye is tailored for intermediatevision (60-80 cm) vision by the induction of positive asphericity. Inparticular embodiments, one eye is tailored for near vision (30-40 cm)vision by the induction of negative asphericity and the other eye istailored for near vision (30-40 cm) vision by the induction of positiveasphericity.

In some examples, the amount of induced asphericity of the lens istailored to compensate for the spherical aberration of the cornea. Inother examples, the amount of induced asphericity of both lenses aretailored to compensate for the spherical aberration of their respectivecorneas. In alternate examples, one lens is adjusted to remove thespherical aberration of the entire eye and the other lens is adjusted toinduce asphercity for intermediate vision (60-80 cm). In some examples,one lens is adjusted to remove the spherical aberration of the entireeye and the other lens is adjusted to induce asphercity for near vision(30-40 cm).

Additional Embodiments

FIGS. 13A-B illustrate that, in order to address the above describedneeds, embodiments of a Light Adjustable Lens (LAL) 100 can comprise acentral region 110, centered on a central axis 112, and a peripheralannulus 120, centered on an annulus axis 122 and surrounding the centralregion 110, wherein the central axis 112 is laterally shifted relativeto the annulus axis 122 and the LAL axis 102.

FIGS. 13C-D show steps of a light adjustment procedure that can be usedto form the LAL 100 of FIGS. 13A-B. As shown in FIG. 13C, in typicalembodiments the annulus axis 122 can be centered on the LAL axis 102, oron the center of the dilated iris 5. (The dilated/non-dilated status ofthe iris 5 is indicated in the Figures.) At this stage, a firstillumination 222 can be applied to form the peripheral annulus 120, witha peripheral optical power 124, in the LAL 100, centered on the annulusaxis 122. In some embodiments, the peripheral annulus 120 can bepre-molded into the LAL 100, instead of being formed after implantation.FIG. 13D shows that next, the central axis 112 can be centered on avisual axis 132 of the eye, e.g., after the iris 5 returned to itsnon-dilated state. Subsequently, a second illumination 242 can beapplied to form the central region 110, with a central optical power114, centered on this central axis 112, in order to optimize the opticalperformance of the LAL 100. In this procedure, the central axis 112often ends up shifted relative to the annulus axis 122 and the LAL axis102 for several reasons, including the following.

(1) First, during the surgical planning process, the doctor may have notselected the optimal, most centered position for the LAL 100.

(2) In other cases, the surgeon may have ended up implanting the LAL 100in a position shifted from the presurgical planned position.

(3) In yet other cases, after the implantation, the LAL 100 may haveshifted, or tilted away from its planned position, as shown in FIGS.13C-D.

(4) Finally, the first illumination 222 is often applied with the iris 5being dilated, to create the peripheral annulus 120 large enough toprovide the desired optical performance even when the iris 5 is in itsmost dilated state. In contrast, the considerably smaller central region110 is preferably formed with a non-dilated iris 5, in order to centerit on the visual axis 132 with high precision. This is so because theoptical performance of the small central region 110 deterioratesnoticeably if it is not aligned with the visual axis 132 well. Andfinally, since the iris 5 often does not dilate in a uniform, concentricmanner, the center of the relaxed, non-dilated iris 5 is often shiftedrelative to the center of the dilated iris 5, and therefore, the centralaxis 112 is often shifted relative to the annulus axis 122.

The shift of the central axis 112 relative to the annulus axis 122 willbe sometimes abbreviated as axis shift 111. In embodiments of the LAL100, the axis shift Ill can be captured in various ways. In absoluteterms, the axis shift 111 can exceed 0.1 mm. In some embodiments, theaxis shift 111 can exceed 0.2 mm. In yet other embodiments, the axisshift Ill can exceed 0.5 mm. In relative terms, the axis shift 11 canexceed 5% of the diameter of the central region 110. In someembodiments, the axis shift 111 can exceed 10% of the diameter of thecentral region 110. In yet others, it can exceed 20% of the diameter ofthe central region 110. Finally, in manufacturing terms, the axis shift111 can exceed a manufacturing radius-tolerance of the LAL 100 by 20%.In other embodiments, the axis shift 111 can exceed the manufacturingradius-tolerance of the LAL 100 by 50%. This definition captures thatthe axis shift 111 is not an accidental, or tolerance-induced unintendedshift of a pre-molded multifocal IOL, but an intended shift, exceedingthe manufacturing tolerance.

FIG. 13A illustrates the optical power of the LAL 100 as a function of aradius r. The radius can be measured from a LAL axis 102. The centralregion 110 can have a position-dependent central optical power 114, theperipheral annulus 120 can have a position-dependent peripheral opticalpower 124. In embodiments, an average of the central optical power 114can be at least 0.5 diopter different from an average of the peripheraloptical power 124. In some embodiments, the average of the centraloptical power 114 can be at least 1.0 diopter different from the averageof the peripheral optical power 124. Since the central axis 112 isshifted relative to the annulus axis 122, which itself may be shiftedrelative to the LAL axis 102, the central region 110 may be off a centerof the LAL 100, as shown.

The embodiments of the LAL 100 blend various aspects of the EDOF and theCNA IOLs, since the LAL 100 has both a radially varying optical power,thus giving rise to an EDOF, as well as a central region 110, sometimesreferred to as CNA region 110, and is thus shares some of the attributesof a multifocal lens. For this reason, embodiments of the LAL 100 willbe interchangeably also referenced as a blended LAL 100.

FIG. 13B illustrates the same regions of the LAL 100, from a perspectivealong the LAL axis 102 of the LAL 100. In some embodiments, the LAL axis102, the central axis 112, and the annulus axis 122 can all bedifferent. In some typical embodiments, the LAL axis 102 and the annulusaxis 122 can at least approximately coincide, and the central axis 112can be shifted relative to both the LAL axis 102 and the annulus axis122, as shown.

The position dependent optical power is typically induced byilluminating the LAL 100 by applying a suitable illumination pattern.The edge of the illumination pattern, a pattern edge 126 is also shownin FIGS. 13A-B, as a perimeter. Such blended LALs 100 can provideimprovements for the above described medical problems at least asfollows.

(1) After the LAL 100 is implanted and settles in the patient's eye, thecentral axis 112, and thus the central, or CNA region 110 can becentered with the visual axis 132 of the eye with the iris 5 being in anon-dilated state. It is recalled that the visual axis 132 of the eyewith the iris 5 being in its non-dilated state often differs from eitherthe geometrical LAL axis 102 of the LAL 100, and from the visual axis ofthe eye with the iris 5 in its dilated state. Therefore, a method thatdetermines the eye visual axis 132 only after the LAL 100 has shiftedand settled in the eye, and after the iris 5 returned to itsapproximately non-dilated state, and only then applies the secondillumination 242 centered on the central axis 112 that is aligned withthe eye visual axis 132, is an efficient method to center the CNA region110 properly. In the resulting blended LAL 100, the central axis 112often ends up laterally shifted relative to the annulus axis 122, as wasdescribed in relation to FIGS. 13A-B. Thus, the described embodiments ofthe blended LAL 100 are capable of overcoming the above-mentionedde-centering challenge of pre-formed multifocal/CNA IOLs, and avoid theshift-induced aberrations, such as coma.

(2) Since the near vision capability of these blended LALs 100 isprimarily delivered by the CNA/central region 110, the peripheralannulus 120 can be formed with a considerably smaller radial variationof the peripheral optical power 124, which thus extends the depth offocus only to a considerably smaller degree. Therefore, the blurrinessand aberrations, caused by the peripheral annulus/EDOF region 120 of theblended LAL 100 is substantially less than in an EDOF-only IOL/LAL.

(3) The same reduction of the radial variation of the optical power inthe blended LAL 100 causes the effective optical power, experienced bythe patient, to vary less with the radius of the iris 5. This reducesanother source of patient discomfort, and thus is a further medicalbenefit.

(4) In some blended LALs 100, the radial variation of the peripheraloptical power 124 can be selected to induce a spherical aberration thatcompensates a spherical aberration caused by the cornea of the eye. Thiscompensation can be partial, or an essentially complete compensation.The implantation of such spherical aberration-compensating blended LALs100 can advantageously minimize the imaging aberrations of the entireophthalmic system of the eye.

At least for the above reasons (1)-(4), and for further reasonsarticulated below, the here-described embodiments of the blended LAL 100retain much of the medical benefits of the separate EDOF and the CNAdesigns, while they mitigate and minimize the undesirable side effectsof these designs. These benefits also characteristically distinguish theblended LAL 100 embodiments from the mentioned pre-formed multifocal CNAIOLs, corneal inlays, and CNA contact lens.

With reference to FIG. 13C, the first illumination 222 can have any ofthe illumination patterns described in FIGS. 1-12, as applicable, usedto increase the depth of focus of the implanted LAL. With reference toFIG. 13A and FIG. 14A, the lens materials and lens optical properties ofthe LAL 100 can have any material and property, described in relation toFIGS. 1-12, as appropriate.

In the embodiments illustrated in FIGS. 13-19, the average of thecentral optical power 114 is at least 0.5 diopter higher than theaverage of the peripheral optical power 124. In some embodiments, thecentral optical power 114 is at least 1.0 diopter higher than theaverage of the peripheral optical power 124. As such, the central region110 is adapted to provide improved near vision, and the peripheralannulus 120 provides improved distance vision. In the embodiments ofFIGS. 20A-C, the average of the central optical power 114 is at least0.5 diopter lower than the average of the peripheral optical power 124.In some embodiments, the average of the central optical power 114 is atleast 1.0 diopter lower than the average of the peripheral optical power124. In these embodiments, the central region 110 is adapted to provideimproved distance vision, and the peripheral annulus 120 providesimproved near vision. Thus, the central region 110 can be called aCentral Near Add (CNA) region 110 for the embodiments of FIGS. 13-19,while for the embodiments of FIGS. 20A-C, the central region 110 can bereferred to as Central Distance Add (CDA), or Peripheral Near Add (PNA)region. These latter phrases are less widely used.

In all the embodiments of FIGS. 13-30, the term “average” can be definedin various suitable manners. For example, the average can refer to anarea integral of the optical power. In some cases, only a portion, orfraction, of the total area of the central region 110 and the peripheralannulus 120 can be used to compute the average as an area integral. Suchfractional definitions of the average can be useful to de-emphasize, ordisregard non-representative deviations close to the pattern edge 126,or close to the region separating the central region 110 from theperipheral annulus 120. The fractional area can be at least 25% of thetotal area of either the central region 110, or the peripheral annulus120. In other embodiments, this can fractional area can be 50%, 75%, or90%. In other cases, the average can be defined along a representativecircle, or over a band, or with a weighting function, or as a moment ofa certain order of the optical power.

FIGS. 14A-B illustrate the position of these regions relative to thephysical structure of the LAL 100. Prior to forming the peripheralannulus 120 and the central region 110 in the LAL 100 by illuminations222/242, the front and rear surfaces of the LAL 100 typically have asingle, approximately constant curvature, and, accordingly, have anoptical power that is either independent of the position, or depends onit very weakly, only due to the finite thickness of the LAL 100, forexample.

After the LAL 100 is formed by applying a first illumination 222 to formthe peripheral annulus 120, and then by applying a second illumination242, to form the central region 110, the central axis 112 is oftenshifted relative to the LAL axis 102, in order to compensate for thepostsurgical shift and tilt of the LAL 100 that misaligned the LAL axis102 with the visual axis 132 of the eye with the iris 5 in itsnon-dilated state. Sometime the annulus axis 122 also ends up beingshifted relative to the LAL axis 102. In the shown example, the centraloptical power 114 and the peripheral optical power 124 meet at a sharpboundary. In other examples, a smoother transition optical power 134 ofa transition 130 can be between them.

FIG. 14B shows the LAL 100 of FIG. 14A, from the perspective of the LALaxis 102, the relative positions of the central region 110 and theperipheral annulus 120, and the central axis 112 being shifted relativeto the annulus axis 122 by the axis shift 11.

The physical structure of the LALs 100 includes a lens edge 146,continuing in a LAL rim 148 to a LAL rim edge 149. The haptics 105protrude well beyond the LAL rim edge 149, to wedge and to stabilize theLAL 100 into the capsular bag emptied by the cataract surgery. Thepattern edge 126 of the first illumination 222 typically does not reachall the way to the lens edge 146, it stops just before it. In someembodiments, the pattern edge 126 may coincide with the lens edge 146,or even extend to the LAL rim 148, that is initially flat and thus hasno optical power. The LAL 100 typically also includes a UV (i.e.ultra-violet illumination) absorbing layer 127. The first and secondilluminations 222/242 are applied from the side of the LAL 100 oppositeof this UV absorbing layer 127. A role of this UV absorbing layer 127 isto reduce the transmitted portion of the illuminations to completelysafe levels.

FIGS. 13A-B and FIGS. 14A-B further illustrate that the LAL 100 can alsoinclude a transition 130, between the central region 110 and theperipheral annulus 120. The transition 130 can have a transition opticalpower 134 that changes from the central optical power 114 to theperipheral optical power 124. The overall difference between the centraloptical power 114 and the peripheral optical power 124 will sometimes bereferred to as an optical power change 136.

The double wavy lines indicate that the LAL 100 has an additional,“base” optical power in the 5-35 diopters range, typically within a fewdiopters of 20 diopters, whereas the position dependent peripheraloptical power 124 may vary 0.5-2 diopters in the peripheral annulus 120,the transition optical power 134 may vary 0.5-2 diopters in thetransition 130, and the central optical power 114 may vary 0.1-1diopters in the central region 110, as an illustration. Broader rangescan be employed in some embodiments. To avoid making the curve of theposition dependent optical powers 114, 124, and 134 uninformatively flatrelative to the much larger base optical power of 10-30 D, this baseoptical power has been suppressed in the applicable Figures, and onlyindicated with the double wavy line. In other words, the optical poweraxis has been largely compressed in the relevant Figures, such as inFIG. 13A.

FIGS. 15A-C illustrate the results of measurements of the optical poweras a function of the radial distance of the blended LAL 100 in the mainstages of the formation process, as indicated in FIGS. 13C-D. Suchoptical power measurements can be performed by several known methods andapparatuses, such as wavefront measurement systems, and aberrometers,especially Shack-Hartmann wavefront sensors, among others.

FIG. 15A shows the radially varying optical power prior to the firstillumination 222 in a LAL 100 that has a pre-molded radially varyingoptical power, causing a spherical aberration. The optical power OPvaries from about OP=19.2 D at the lens edge 146 at around r=2.3 mm toOP=21.2 D at r=0, the LAL axis 102, yielding an about 2 D radial opticalpower variation: ΔOP=2D.

FIG. 15B illustrates the result of the same optical power measurementafter the first illumination 222 has been applied, centered on anannulus axis 122, which in this case was chosen to coincide with the LALaxis 102. At the lens edge 146 the OP got enhanced to 20.8 D, while atthe center to 22.8 D. Thus, the first illumination 222 increased theaverage optical power of the LAL 100 by about 2 D, while preserved theradial optical power variation at ΔOP=2D in this case.

FIG. 15C shows the radially varying optical power of the blended LAL 100after the second illumination 242 has been also applied to induce a CNAin a central region 110. The second illumination 242 was centered on acentral axis 112 that was shifted from the annulus axis 122, as shown.Visibly, the overall LAL optical power is a function of the radius inthese blended LALs 100, and thus so is the overall focal distance.Accordingly, these blended LALs 100 can be characterized as “polyfocalIOLs”, or “polyfocal LALs 100” as well.

In FIG. 15C, the central, or CNA, region 110 was formed over a diameterof 1.5 mm. Within this central region 110 the central optical power 114is often intended to be quite smooth. FIGS. 15A-C illustrate a precisionof the above numerical values and ranges, caused by natural measurementuncertainties and variations. The variations of the optical powermeasurements are high for small radii and decrease with increasingradius because the accuracy of the measurement of a region's opticalpower is set by the area of the region, and thus the variations areinversely proportional to this same area. The quadratically smaller areaof the central region 110 compared to the peripheral annulus 120explains that the fluctuations of the measured central optical power 114are visibly greater than that of the peripheral optical power 124. FIG.15C illustrates that in some embodiments, measurements of the centraloptical power 114 will exhibit an optical power variation 115, of 0.2 D.In other cases, the optical power variations 115 in the central opticalpower 114 can be up to 0.4 D. FIG. 16 illustrates that in someembodiments the central optical power 114 can have an optical powervariation 115 of a few tenth of diopters that arises not frommeasurement-related fluctuations, but from the smooth curving centraloptical power 114.

In some embodiments of the LAL 100, the central region 110 can directlymeet the peripheral annulus 120 at a well-defined boundary, making thetransition 130 a sharp boundary; and the central region 110 and theperipheral annulus 120 can meet at this sharp boundary.

FIG. 13A, FIG. 15C and other Figures show that in some otherembodiments, the transition 130 can be a smoother transition annularregion between the central region 110 and the peripheral annulus 120.The smoothness of the transition 130 can be captured via ratios ofrelevant radii. FIG. 15C illustrates such relevant radii: a radial widthof the transition 130, ΔRT 154, and an outer radius RT 152 of thetransition 130. In some embodiments, the ratio ΔRT/RT can be less than0.3. In other embodiments, ΔRT/RT can be less than 0.5, in yet others,less than 0.7. Here, a typical value for a radius RC 156 of the centralregion 110 can be in the range of 0.5 mm to 1.0 mm in some embodiments.

It is noted that statements and numerical ranges of the opticalproperties, such as the optical power and the spherical aberration, aremeant within a context and a measurement protocol, since these opticalproperties of the LAL 100 can be measured in different ways, followingdifferent protocols that result in different values.

(1) In one protocol, the LAL 100 can be characterized in isolation, onan optical bench, where the LAL 100 is typically immersed into a salinesolution to mimic its optical performance in the aqueous of the eye.Such measurements can be set up at least in the following ways. (1a)Starting with a LAL 100 that has not been light adjusted yet; thenperforming a light adjustment illumination protocol as defined by theLAL manufacturer, and then measuring the optical characteristics of thelight-adjusted LAL 100 on the optical bench. (1b) Implanting the LAL 100into a patient's eye; then performing the light adjustment illuminationprotocol in the eye; then explaining the light-adjusted LAL 100 from thepatient's eye; and finally, measuring the optical characteristics of theexplanted LAL 100 again on the optical bench.

(2) In another protocol, the LAL 100 can be characterized “in situ”, aspart of the overall ophthalmic optical system that includes the LAL 100and the cornea that has its own optical power and own sphericalaberration, the two lenses separated by a space filled by the aqueous ofthe anterior chamber of the eye. Defining such an “in situ” protocol canbe particularly useful if the optical power of an implanted LAL needs tobe determined without explaining the LAL from the patient's eye. Here wealso describe two related optical measurement approaches.

(2a) In the in situ protocol, the optical power of the cornea 15, P_(c),and the optical power of the LAL, P_(LAL), combine into the overallophthalmic power P_(o), according to the known formulae of two lens(telescopic) systems:

P _(o) =P _(c) +P _(LAL) −d*P*P _(LAL) =P _(c)+(1−d*P _(c))*P_(LAL)  (3)

where d is the separation between the cornea 15 and the LAL 100. Usingtypical values of P_(c) about 40-45 D and d about 7 mm, a 1 D change inthe optical power 1).4r, in the LAL plane approximately translates to anabout 0.7 D change in the overall optical power P_(o) in the cornealplane, defined approximately as a plane at the vertex of the cornea 15.

Eq. (3) establishes a translation scheme between the different types ofoptical power measurements. For example, if the LAL optical power Put isadjusted by 1 D on the optical bench, the adjusted LAL can be expectedto cause an about 0.7 D change of the ophthalmic optical power P_(o),when implanted in the eye. And in reverse, if a light adjustmentprocedure is carried out on an implanted LAL that is measured to cause a1 D change of the ophthalmic optical power P_(o) in the corneal plane,and then the LAL is explanted, the explanted LAL optical power P_(LAL)can be expected to show a power change of about 1 D/0.7=1.43 D in theLAL plane.

(2b) Eq. (4) below shows that the optical power of the entire eyeophthalmic optical system can be also calculated with an analysis thatincludes more parameters and details, such as additionally capturingbeam propagation from the cornea to the separately located spectacleplane. Eq. (4) below shows the change in power of the implanted LAL,ΔP_(LAL), necessary to achieve a specific refractive correction of theeye at the spectacle plane, R, determined as the refractive correctionneeded after the LAL 100 has been implanted into the eye. With thenotation of protocol (2a), R_(x)=ΔP_(o):

$\begin{matrix}{{\Delta \; P_{LAL}} = {n_{Aq}\left( {\frac{1}{\frac{n_{Aq}}{\frac{1}{\frac{1}{R_{x}} - d_{v}} + P_{c}} - d_{ELP}} - \frac{P_{c}}{n_{Aq}P_{c}d_{ELP}}} \right)}} & (4)\end{matrix}$

Here, n_(Aq) is the refractive index of the human aqueous, P is thecorneal optical power, d_(ELP) is the distance from the apex of thecornea to the back principal plane of the implanted LAL 100, and d_(v)is the vertex distance, i.e. distance from the cornea to the spectacleplane. Typical values in Eq. (4) include a corneal power P=45 D,d_(ELP)=4.5×10⁻³ m, and n_(Aq)=1.336. With these parameters, a desiredrefractive correction R_(x)=+1.5 D translates to a change in LAL powerof ΔP_(LAL)=+2.14 D. Taking the ratio of the desired spectacle planerefractive correction R_(x)=+1.5 D, to the required change in LAL power,ΔP_(LAL)=+2.14 D, results in a translation ratio of 0.70. This ratioessentially agrees with the 0.7 translation ratio determined from Eq.(3). Patient-to-patient variations of the above parameters can lead to aplus-minus 3% variation of this translation factor of 0.7. In otherembodiments, to a plus-minus 5% variation, or plus minus 10%/ovariation.

Translation factors can be derived for the other optical characteristicsas well. For example, the spherical aberration, SA, depends notably onthe measurement diameter, aperture, or pupil. (1) For isolated LALs, anatural definition of this pupil is in the plane of the LAL. (2)However, for implanted LALs, the SA cannot be directly measured at theLAL plane, and therefore a natural definition of the pupil is in thecorneal plane. From this, the LAL-plane SA can be derived. A conversion,or translation factor can be established between these two measurementpositions based on recalling the followings.

(2.1) The SA scales with the fourth power of the diameter, and (2.2) abeam that is collimated at the cornea is focused down by the cornealoptical power P_(c) to a decreasing diameter as it propagates toward theimplanted LAL. Using a representative corneal power of P_(c)=45 D, adiameter of a collimated beam incident on the corneal plane gets reducedby about a factor of 0.85 by the time it reaches the LAL plane.Equivalently, a diameter of a beam propagating from the LAL out to thecornea increases by a factor of 1/0.85. Thus, e.g., a corneal beamdiameter of 6 mm gets focused down to a 5.1 mm LAL-plane beam diameter,and a corneal beam diameter of 4.7 mm gets focused down to a 4.0 mmLAL-plane beam diameter. It is customary to characterize the SA valuesof contact lenses, positioned on the cornea, at a d=6 mm diameter. It isalso customary to characterize IOL SA values at a diameter of 4 mm,which is, however, less than the diameter of a down-focused 6 mm beam.Therefore, translating the d=6 mm corneal SA values into d=4 mm IOL SAvalues involves two conversion steps: the down-focus factor of 0.85, andthe ratio of diameters to the fourth power. Thus, a LAL/IOL plane SAvalue, measured at 4 mm diameter is to be converted to the diameter of5.1 mm that corresponds to the 6 mm corneal diameter by thedown-focusing factor of 0.85. As a relevant example, since (5.1 mm/4mm)y 2.6, a SA value of SA=0.1 μm at a 4 mm LAL-plane diametercorresponds to a SA=0.26 μm at a 6 mm corneal-plane diameter. Forpatient corneas with different corneal optical power, thiscorrespondence factor can fall within a range around 2.6, such as in therange of 2.2-3.0, in other cases, 2.4-2.8.

(3) The above SA values characterize the light adjusted region. Withreference to FIGS. 13A-B, 14A-B, this light adjusted region extends tothe pattern edge 126, typically inside the LAL rim edge 149. Since theshape of the LAL 100 continues to change outside the pattern edge 126,SA values that are measured with diameters past the pattern edge 126 areimpacted by the LAL rim 148, and tend to be different from SA valuesmeasured at diameters inside the pattern edge 126. In some cases, the SAcan even change sign when measured with the rim included.

In some blended LAL 100 s, it can be medically beneficial for thecentral optical power 114 to have only a limited spatial variation, anda corresponding approximately flat position-dependence, since limitingspatial variations limits the aberration of the imaging, and thusimproves the visual acuity. In these “flat top” embodiments, the centralregion 110 can have an optical power variation less than 0.2 dioptersover 50% of the central region 110, resulting in high visual acuity. Inother embodiments of blended LALs 100, the central optical power 114 canbe a function of a radius from the central axis 112, having an opticalpower variation 115 greater than 0.2 diopters over 50% of the centralregion 110. These embodiments may be emphasizing the presbyopiamitigation benefit.

Analogously, in some embodiments of the LAL 100, the peripheral opticalpower 124 can have an approximately flat position-dependence, having anoptical power variation less than 0.2 diopters over 50% of theperipheral annulus. In related embodiments, the peripheral optical power124 can be a function of a radius from the annulus axis 122, having anoptical power variation greater than 0.2 diopters over 50% of theperipheral annulus.

FIGS. 17A-B and 18 illustrate how the LAL 100 with the abovecharacteristics mitigates the presbyopic medical needs, describedearlier. One of the most widely used measure of a patient's vision isthe Visual Acuity (VA), which records the ratio of a distance a patienthas to stand from an eye chart to achieve the same visual clarity as aperson with normal eyes achieves from 20 feet. There are closely relatedconventions to determine this VA value, such as the Snellen VA and theEarly Treatment Diabetic Retinopathy Study (ETDRS) VA. Another measureis the log MAR, where “MAR” abbreviates “Minimal Angle Resolved”, and“log” references that the logarithm of this angle is taken for thismeasure. These measures are determined based on the subjective feedbackof the patient, typically by asking the patient to report which lettersin which lines he/she can see clearly on the eye chart, from differentdistances. In practice, changing the viewing distance is often simulatedby inserting lenses of varying diopters in front of the patient, using aphoropter. Typically, these tests are reported after incorporating acorrection to infinite viewing distances. Thus, in FIGS. 17A-B and FIG.18, 1D corresponds to a viewing distance of Im, etc. These two measurescan be translated to each other, as shown in Table 8:

TABLE 8 VA logMAR 20/40 0.3 20/32 0.2 20/25 0.1 20/20 0.0 20/16 −0.120/12.5 −0.2 20/10 −0.3

It is customary to accept log MAR values smaller than 0.2 (i.e. VAvalues better than 20/32), as indications of good, or satisfactoryvisual acuity. (Following convention, the negative log MAR values are atthe top of the axis, and they grow to positive lorMAR values at thebottom of the axis. Therefore, log MAR values “smaller than 0.2” are infact above the log MAR=0.2 line in FIGS. 17-18.) With this preparation,FIGS. 17A-B and 18 demonstrate the problem of presbyopia and theimproved visual acuity delivered by the blended LALs 100. A young eyehas an easily deformable crystalline lens, and therefore can accommodateto a wide range of viewing distances. This is seen in FIG. 17A by thebase of the log MAR curve, i.e. the range of diopters with log MARvalues smaller than 0.2, covering the wide range from +1.5 D to −2.5D.In viewing distances, this translates to good visual acuity from(1/2.5D)=40 cm out to infinity, and beyond, to virtual targets. In termsof a depth of focus, or DOF, this young eye exhibits aDOF(young)=+1.5D−(−2.5D)=4D.

An older, presbyopic eye is gradually losing its ability to accommodateto different viewing distances. Presbyopia is, in fact, Greek for “oldeyes”, or “old sight”. E.g., the DOF of the shown presbyopic eyedecreased to DOF(presbyopic)=+0.5D−(−0.5D)=1D, approximately.

FIG. 17B illustrates the two presbyopia solutions, discussed earlier.(1) IOLs with an Extended Depth of Focus, or EDOF IOLs are formed with aradially varying optical power that extends the focal point into anelongated focal region. The adaptiveness of the human vision enables thepatient's brain to extract images created with this elongated focalregion, to see targets in a wider range. This adaptiveness smoothlybroadens the log MAR curve, extending the DOF toDOF(EDOF)=+0.5D−(−1.5D)=2D.

(2) IOLs with a Central Near Add (CNA) introduce a more distinctlydefined second focal region, and thus broaden the log MAR curve unevenlyby introducing a second maximum. The illustrated CNA IOL has aDOF(CNA)=+0.5D−(−2.5D)=: 3D, approximately. While both of thesepresbyopic techniques extend the DOF and thus mitigate presbyopia byimproving visual acuity over an extend range of target distances, theydo so by introducing drawbacks, as was discussed earlier.

The log MAR curve articulates these drawbacks further. EDOF IOLs extendthe DOF to a medium degree. CNA IOLs extend the DOF better than EDOFIOLs, DOF(CNA)>DOF(EDOF). However, they do so at the expense of anoticeable reduction of the midrange visual acuity, as shown by thepronounced log MAR minimum around −0.5D.

FIG. 18 illustrates the log MAR curve of the blended LALs 100, whichblend the EDOF and the CNA techniques. (1) Visibly, the blended LALs 100extend the medium DOF of the EDOF IOLs from DOF(EDOF)=2D to the longerDOF of the CNA IOLs: DOF(EDOF+CNA)−=3-3.5D. (2) Importantly, the blendedEDOF+CNA LALs 100 also largely eliminate the midrange log MAR minimum ofthe CNA IOLs. To sum, the blended EDOF+CNA LALs 100 deliver the longerDOFs of the CNA IOLs, as well as the no-midrange-minimum smoothness ofthe EDOF IOLs. In other words, blended LALs 100 deliver the positives ofthe two existing presbyopia IOLs, while eliminating their drawbacks.

FIGS. 13-18 illustrated blended LALs 100, where (1) the central opticalpower 114 was higher than the peripheral optical power 124, at least inan average sense. Also, the optical power was a decreasing function ofthe radius (2) in the central region 110, and (3) in the peripheralannulus 120, shown by the downward curvatures of the optical powercurves in both of these regions. These three design factors (1)-(3) canbe combined in 2³=8 different ways, defining 8 possible embodiments ofthe blended LALs 100. All 8 combinations can offer advantages for visualchallenges.

FIGS. 19 and 20A-C illustrate four of these eight possible combinationsof the design factors. In FIG. 19, the central optical power 114 isstill greater than the peripheral optical power 124, and the centraloptical power 114 still has a downward curvature. However, theperipheral optical power 124 has an upward curvature. Such opticaldesigns also have an extended depth of focus, but the geometric relationbetween light rays from larger radii and smaller radii is reversed. Inthis design, the peripheral annulus 120 does not extend the depth offocus beyond the DOF extension induced by the central region 110.Instead, an advantage of the design of FIG. 19 is that it “fills in” themidrange log MAR minimum even more efficiently than previously describeddesigns, thereby delivering an improved overall visual acuity.

FIGS. 20A-C show three embodiments, where the central optical power 114is less than the peripheral optical power 124, at least in the abovedefined average sense. In these LALs 100, the central region 110 isproviding good distance vision and the peripheral annulus 120 providesgood near vision. In this sense, these embodiments and designs can becalled Central Distance Add (CDA) LALs, or Peripheral Near Add (PND)LALs. These are less frequently used terms, as mentioned before.

In FIG. 20A, the central optical power 114 and the peripheral opticalpower 124 are both decreasing functions of the radius. In FIG. 20B, thecentral optical power 114 increases with the radius, while theperipheral optical power 124 decreases with the radius. In FIG. 20C, thecentral optical power 114 and the peripheral optical power 124 are bothincreasing functions of the radius.

In any of the above embodiments of the blended LAL 100, the centraloptical power 114 can be a quadratic function of the radius from thecentral axis 112 over the central region 110, optionally having a smallcorrection term, or can have a quadratic component. In some of thecases, the peripheral optical power 124 can be a quadratic function ofthe radius from the annulus axis 122 over the annular region 120,optionally with a small correction term, or can have a quadraticcomponent. To characterize these embodiments, it is recalled that theradius dependent optical power P(r) is related to the wavefront W(r) as:

$\begin{matrix}{{P(r)} = {\frac{1}{r}\frac{{dW}(r)}{dr}}} & (5)\end{matrix}$

Therefore, the above-described quadratic functions or components of theoptical power P(r) correspond to a wavefront aberration proportional tothe fourth power of the radius. The simplest fourth order aberration isthe angle independent spherical aberration, or SA, its coefficient oftendenoted by Z(4,0), or Z12 in Zernike notation. Thus, embodiments of theblended LAL 100, where the position dependence of the optical power P(r)has a quadratic function or component, can be also characterized by acorresponding spherical aberration. Below, ranges of the sphericalaberrations SA of some blended LALs 100 will be characterized. Thedescribed SA values can be induced by the peripheral optical power 124alone, or by a combination of the central optical power 114, theperipheral optical power 124, and the transition optical power 134 ofthe blended LAL 100. An example of the former case is a pre-molded LAL100, where a spherical aberration has been molded into the LAL 100,including into its peripheral annulus 120, measured before the centralregion 110 has been formed. An example of the latter case is a LAL 100,where the central region 110 has been already formed, typically afterimplantation.

In some blended LALs 100, the spherical aberration with one of the abovedefinitions can be in the −0.05 μm to −1 μm range at a diameter of 4 mmin a plane of the LAL. In some embodiments, the spherical aberration canbe in the −0.05 μm to −0.35 μm range at a diameter of 4 mm in a plane ofthe LAL In yet other embodiments, the spherical aberration can be in the−0.10 μm to −0.25 μm range at a diameter of 4 mm in a plane of the LAL.

As noted above, these LAL-plane SA values translate to SA valuesmeasured at a 6 mm diameter at the corneal plane approximately by ascale factor of about 2.6, or in a range around 2.6, such as the rangeof 2.4-2.8, or 2.2-3.0. Since the translation factor can vary over thesenarrow, but finite ranges, corneal plane SA values will be expresslydescribed next. This translation of the SA values can be particularlyuseful if the SA of an implanted LAL 100 needs to be determined withoutexplaining the LAL 100 from the patient's eye. For example, the −0.05 μmto −1 μm SA range at a diameter of 4 mm at the LAL plane can translateto an approximately −0.13 μm to −2.6 μm SA range at a diameter of 6 mmin the corneal plane. In other embodiments of the blended LAL 100implanted in an eye, the SA, measured at a 6 mm diameter at the cornealplane, can be in the range of −0.05 μm to −2 μm; in yet otherembodiments, in the range of −0.1 μm to −0.6 μm, or in the range of −0.2μm to −0.4 μm.

As described next, when the spherical aberration is measured in an eyewith an implanted LAL 100, the measurement results will be impacted bythe spherical aberration of the eye before the implantation. Therefore,the SA attributed to the implanted LAL 100 alone is to be extracted fromthe SA values measured for the entire eye.

In the context of measuring the SA of an eye with an implanted LAL 100,it is recalled that the cornea has its own spherical aberrationSA(cornea). Over a large patient population this corneal SA(cornea) hasa distribution. An average, or mean, of this distribution is describedin some studies to be around SA(cornea)=+0.26 μm, with a standarddeviation of about ±0.13 μm at the corneal plane with a 6 mm diameter.Other studies report mean values between +0.20 μm and +0.30 μm, withcorrespondingly varying standard deviation. The SA of the combinedophthalmic optical system of the cornea 15 and the implanted LAL 100will have an SA(combined)=SA(LAL)+SA(cornea), with both SA valuesmeasured at the same plane and radius. For example, if the LAL 100 isknown to have a SA in the range of −0.10 μm to −0.25 μm at a 4 mmdiameter in the LAL plane, then first this SA is to be translated to aSA at a 6 mm diameter in the corneal plane. Using the translationalfactor of 2.6, corresponding to the average corneal power, the SA(LAL,d-4 mm, LAL plane)=−0.10 μm to −0.25 μm range translates to a SA(LAL,d=6 mm, corneal plane)⁼−0.26 μm to −0.65 μm range. Second, the SA of thecombined ophthalmic optical system of the cornea 15 and the implantedLAL 100 can be determined by combining this SA(LAL, d=6 mm, cornealplane) with the SA(cornea) of the cornea at the same 6 mm diameter inthe same corneal plane: SA(combined)=SA(LAL, d=6 mm, cornealplane)+SA(cornea). With the above values, SA(combined) at the 6 mmdiameter in the corneal plane in embodiments can be in the range of 0 μmto −0.39 μm in case of an eye with an average SA(cornea). In otherembodiments, again measured at d=6 mm at the corneal plane, the combinedspherical aberration of an eye with an implanted LAL 100, theSA(combined) can fall within the −0.05 μm to −0.5 μm range. In yet otherembodiments, SA(combined) can fall in the −0.1 μm to −0.2 μm range.

The same consideration can be used in reverse to determine the SA(LAL,d=6 mm, corneal plane) of a LAL 100 implanted into the eye of aparticular patient, by measuring the SA(combined) of the patient's eye,and then subtracting from it the patient's specific corneal SA(cornea).From the so-determined SA(LAL, d=6 mm, corneal plane), the SA(LAL, d=4mm, LAL plane) can then be determined by the above translation factor,as needed.

Another calculus can be useful to reconstruct SA(pre-mold), thepre-molded portion of the SA for an implanted LAL 100, where the CNA, orcentral region 110 has been already formed. This SA(pre-mold) can berelated to the entire LAL 100, or to the peripheral annulus 120. Afterthe implantation of the LAL 100, the SA(pre-mold) is shifted with aASA(CNA) by the formation of the CNA, or central region 110. Therefore,the SA(pre-mold) can be reconstructed by measuring the SA of the entireimplanted LAL 100, and then subtracting appropriate ASA(CNA) values. Insome embodiments, at d=6 mm in the corneal plane, ASA(CNA) can takevalues in the −0.01 μm to −0.4 μm range, in others in the −0.05 μm to−0.2 μm range. The formation of the CAN, or central region 110 oftenshifts the SA(LAL) value relatively little because the diameter of theCAN, or central region 110 is often small, in the range of 0.5 mm to 1.5mm, and the value of the spherical aberration SA scales with the fourthpower of the diameter.

In some embodiments of the blended LAL 100, a spherical aberrationcaused by the position-dependence of the central optical power 114, theperipheral optical power 124, or their combination, can be selected toapproximately compensate a spherical aberration of the cornea 15 of theeye. In such embodiments, the optical aberrations of the combinedoptical system of the cornea 15 and the LAL 100 are minimized.

For completeness, it is mentioned that once the central region 110 andthe transition 130 have been formed, the latter with its fast-changingtransition optical power 134, the optical powers 114/124/134 oftendeviate substantially from a quadratic function of the radius, and thusinduce higher order aberrations beyond the Z(12) spherical aberration.

Another type of aberration, a coma is induced when an IOL with apre-molded spherical aberration (an SA IOL) is shifted off the opticalaxis. In Zernike notation, the coma is represented by the Zernikecoefficient Z8, and the spherical aberration by Z12. A Δx off-axis shiftof an SA IOL induces a coma given by Eq. (6):

$\begin{matrix}{{Z\; 8} = {\frac{2\sqrt{10}\Delta \; x\; Z\; 12}{r}.}} & (6)\end{matrix}$

Embodiments of the LAL 100 can mitigate this coma aberration, even ifthe LAL 100 is shifted off-axis. Using embodiments of the LAL 100 wherethe peripheral annulus 120 is formed only after the LAL 100 settled canpreempt this problem entirely, as the peripheral annulus 120 can beformed with an annulus axis 122 that is centered on the visual axis 132.In some cases, this can be achieved by shifting the annulus axis 122with a shift that is equal and opposite to the Δx off-axis shift of theLAL 100. The peripheral annulus 120 can be centered on the visual axis132, e.g., by registering the visual axis 132 prior to dilating the iris5.

In some embodiments of the blended LAL 100, further aberrations of thepatient's vision can be mitigated. A notable example is that in someLALs 100 the position-dependent central optical power 114 can involve acylinder angular dependence. In some LALs 100 the position-dependentperipheral optical power 124 can involve a cylinder angular dependence.Forming a cylinder in either the central region 110 or in the peripheralannulus 120 can mitigate an existing cylinder in the patient's eye.

FIGS. 21A-B illustrate that some embodiments of the blended LALs 100 caninclude an annular mid-range vision region 150, positioned between thecentral region 110 and the peripheral annulus 120. The mid-range opticalpower 154 of this mid-range vision region can be selected to improvevision at medium ranges, such as at distance around 1 meter. An axis ofthe mid-range vision region 150 can coincide with the LAL axis 102, thecentral axis 112, or the annulus axis 122. In some aspects, themid-range vision region 150 may be viewed as part of the transition 130.

In some embodiments of the LAL 100, the first illumination 222 inducesthe position-dependent peripheral optical power 124, and the secondillumination 242 induces the position-dependent central optical power114 primarily by inducing a shape change of the LAL 100 via activating aphotopolymerization process. In other embodiments, the sameilluminations 222 and 242 induce the optical powers 114 and 124primarily by changing an index of refraction of the LAL 100, in effecttransforming the LAL 100 into a Gradient Index of Refraction, or GradedIndex of Refraction, (GRIN) lens. In yet other embodiments, theilluminations 222 and 242 induce the optical powers 114 and 124 by acombination of shape change and index of refraction change.

FIG. 22 illustrates a unifying aspect of the LALs 100 b depicted inFIGS. 13-21. In broader terms, a Light Adjustable Lens (LAL) 100 b canhave a LAL axis 102 b, and include a light-adjusted region 310 r,centered on an adjustment axis 312, with a position-dependent adjustedoptical power 314; wherein the adjustment axis 312 can be laterallyshifted relative to the LAL axis 102 b. The embodiments of FIGS. 13-21are specific embodiments of this general LAL 100 b design, where, e.g.the adjusted optical power 314 includes the central optical power 114,the peripheral optical power 124, or both. A unifying aspect of theseembodiments is that, because they have an adjusted optical power 314that was formed by adjusting the implanted LAL 100 after it settled andoften shifted from its intended position in the capsular bag, theadjustment axis 312 is laterally shifted relative to the LAL axis 102 b.

To relate the light-adjusted region 310 r to the physical structure ofthe LAL 100 b, beyond a pattern edge 126 b, these LALs 100 b can includea lens edge 146 b, a LAL rim 148 b, and a LAL rim edge 149 b, as inFIGS. 14A-B.

FIG. 23 illustrates a distinct case of a LAL 100 c, where the centralaxis 112 is not shifted relative to the annulus axis 122; instead itcoincides with it. In the shown embodiment of LAL 100 c, the centralaxis 112, the annulus axis 122 and the LAL axis 102 all coincide. Thisembodiment may emerge in multiple ways. One of them is that the visualaxis 132 is determined after the iris 5 approximately returned into itsnon-dilated state, for example, during a subsequent office visit, andthe surgeon found that none of the misalignment mechanisms (1)-(4)shifted the LAL axis 102 from the visual axis 132, and thus the centralregion 110 can be formed centered on the shared central axis 112/LALaxis 102. Another possibility is that for some reason, such as to reducethe number of office visits, the surgeon decides to form the CNA/centralregion 110 while the iris 5 is still dilated, in which case it isreasonable to form the CNA/central region 110 with a central axis 112that coincides with the annulus axis 122. All aspects, details anddescriptions related to the embodiments of FIGS. 13-22 can be combinedwith the blended LAL 100 c of FIG. 23.

FIGS. 24-30 describe methods of light adjustment of the blended LALs100. FIG. 24 shows that a method 200 of adjusting a Light AdjustableLens (LAL) 100 can include the following steps.

-   -   Implanting 210 a LAL 100 into an eye;    -   Applying 220 a first illumination 222 to the LAL 100 with a        first illumination pattern 224 to induce a position-dependent        peripheral optical power 124 in at least a peripheral annulus        120, centered on an annulus axis 122;    -   Determining 230 a central region 110 and a corresponding central        axis 112 of the LAL; and    -   Applying 240 a second illumination 242 to the LAL 100 with a        second illumination pattern 244 to induce a position-dependent        central optical power 114 in the central region 110 of the LAL        100; wherein    -   (250) the central axis 112 is laterally shifted relative to the        annulus axis 122 of the peripheral annulus 120, and    -   (260) an average of the central optical power 114 is at least        0.5 diopters different from an average of the peripheral optical        power 124.

In embodiments of the method 200, the average of the central opticalpower 114 can be at least 1.0 diopter different from the average of theperipheral optical power 124.

In some embodiments, the average of the central optical power 114 can beat least 0.5 diopters higher than an average of the peripheral opticalpower 124. The LALs 100 formed with such embodiments can be calledCentral Near Add, or CNA LALs. In other embodiments, the average of thecentral optical power 114 can be at least 0.5 diopters lower than anaverage of the peripheral optical power 124. The LALs 100 formed withsuch embodiments can be called Central Distance Add (CDA), or PeripheralNear Add (PNA) LALs.

In some embodiments of the method 200, the applying 220 of the firstillumination 222 can include applying the first illumination 222 with afirst illumination pattern 224 to induce the position-dependentperipheral optical power 124 in a light-adjusted region that includesthe peripheral annulus 120 and the central region 110. In otherembodiments, the first illumination pattern 224 is concentrated mostlyon the peripheral annulus 120, and an amplitude of the firstillumination pattern 224 can be greatly reduced in the central region110.

As described in relation to FIGS. 13-23, an advantage of the design ofthe blended LAL 100 is that its central axis 112 can be aligned with theeye's visual axis 132. Accordingly, in embodiments of the method 200,the determining 230 of the central axis 112 can include identifying thevisual axis 132 of the eye as the central axis 112.

FIGS. 25A-B illustrate that, since the iris 5 can return to itsnon-dilated state in an asymmetric manner, this determining step 230 ofthe central axis 112 can be performed with an iris 5 of the eye beingin, or returned to, a non-dilated state in order to achieve a goodalignment with the visual axis 132. In related embodiments, the eye doesnot need to fully return to its non-dilated state. In these embodiments,the determining 230 of the central axis 112 can include determining thecentral axis 112 with the iris 5 of the eye being dilated to aniris-radius no more than 30% greater than a non-dilated iris-radius. Inother words, to perform the determining 230 when the iris is only in theprocess of returning to its non-dilated state, but the return is onlypartial and the iris did not reach the non-dilated state fully.

In some other embodiments of the method 200, the determining 230 of thecentral axis 112 can include determining the central axis 112 before theiris 5 of the eye is dilated and registering the determined central axis112 with a feature of the eye. In these embodiments the determined andregistered central axis 112 can be reconstructed after the iris isdilated, but before the applying 240 of the second illumination 242. Insome cases, the registration of the determined central axis 112 can becarried out with respect to retinal features, in other cases, withrespect to features of the iris, limbus, or sclera of the eye. Thedetermining of the central axis 112 can involve determining the visualaxis 132 of the eye with the iris 5 being non-dilated, and then simplydefining the central axis 112 as the determined visual axis 132. Anadvantage of this approach is that the doctor does not have to waitduring the surgery for the iris 5 to slowly return to its largelynon-dilated state; or, does not have to schedule a separate subsequentprocedure to apply the second illumination 242.

In this embodiment of the method 200, the sequence of the applying 220of the first illumination 222 and the applying 240 of the secondillumination 242 can be interchanged, since the availability of theregistered central axis 112 eliminates the need to wait for the iris 5to relax after the applying 220. The sequence of the applying step 220and the applying step 240 can be also interchanged in embodiments of themethod 200 where the iris 5 is dilated not at the beginning of theprocedure, but only after the firstly-performed applying 240 of thesecond illumination 242 has been completed. Finally, in someembodiments, the applying 240 of the second illumination 242 can beperformed before the applying 220 of the first illumination 222, bothwith the iris dilated. In these embodiments, it may be somewhatchallenging to align the central axis 112 with the visual axis 132.

As shown in FIGS. 13-23, the applying 220 of the first illumination 222and the applying 240 of the second illumination 242 can induce atransition 130 between the central region 110 and the peripheral annulus120, having a transition optical power 134 that changes from the centraloptical power 114 to the peripheral optical power 124.

FIG. 16 illustrates that the method 200 can be performed to create “flattop” blended LALs 100. In these LALs 100 the central optical power 114can have an approximately flat position-dependence, having an opticalpower variation less than 0.2 diopters over a central 50% of the centralregion 110. In some other embodiments, the central optical power canhave an optical power variation greater than 0.2 diopters over thecentral 50% of the central region 110.

As before, the central optical power 114 can be a quadratic function ofthe radius from the central axis 112 over a quadratic central region,optionally having a small correction term. As described in relation toEq. (5), such a quadratic radius dependence of the optical power inducesa fourth order spherical aberration, discussed further below.

Also, in some embodiments, the peripheral optical power 124 can have anapproximately flat position-dependence, having an optical powervariation less than 0.2 diopters over 50% of the peripheral annulus 120.In other embodiments, the peripheral optical power 124 can be a functionof a radius from the annulus axis 122, having an optical power variationgreater than 0.2 diopters over 50% of the peripheral annulus 120. Theperipheral optical power 124 can be a quadratic function of the radiusfrom the annulus axis 122 over a quadratic annular region, optionallywith a small correction term.

The mentioned quadratic radius dependence of the peripheral opticalpower 124 can also induce, or cause, a spherical aberration (SA) in the−0.05 μm to −1 μm range at a diameter of 4 mm in a plane of the LAL 100.In some embodiments, the spherical aberration caused by theposition-dependence of the peripheral optical power 124 can be in the−0.10 μm to −0.25 μm range at a diameter of 4 mm in a plane of the LAL100. These LAL-plane, d=4 mm diameter SA values can be translated intocorneal plane, d=6 mm SA values with a translation factor, which in awide class of cases is about 0.26, as calculated earlier.

In some embodiments of the method 200, at least one of the centraloptical power 114 and the peripheral optical power 124 can be selectedsuch that a spherical aberration caused by the position-dependence ofthe selected central optical power 114 or peripheral optical power 124approximately compensates a spherical aberration of the cornea 15 of theeye. As described before, such a selection can minimize, or eveneliminate, the inducing of aberrations in the eye's optical system, by apostsurgical shift of the LAL 100.

In embodiments of the method 200, the applying 220 of the firstillumination 222, or the applying 240 of the second illumination 242 canfurther include inducing the position-dependent central optical power114 with a cylinder angular dependence, or inducing theposition-dependent peripheral optical power 124 with a cylinder angulardependence. These embodiments of the method 200 can mitigate not onlypresbyopia, but also cylinder aberrations of the eye. The inducing of acylinder in the central region 110 or in the peripheral annulus 120 canbe performed before, simultaneously, or after the applying steps 220 or240. The numerous sequences and combinations of the (1) applying 220 ofthe first illumination 222; (2) applying 240 of the second illumination;and (3) inducing the cylinder, can all be embodiments of the method 200.

In some embodiments of the method 200, the applying 220 of the firstillumination 222 and the applying 240 of the second illumination 242 canbe separated by less than 48 hours. In some embodiments, these twoapplying steps 220 and 240 can even be performed as part of a single,integrated procedure, separated by only a short time, thus reducing thedemands on the surgeon and the patient.

Also, once all the light adjusting steps of the method 200 have beenperformed, a lock-in illumination can be applied to the LAL 100, inorder to lock in the induced peripheral optical power 124 and theinduced central optical power 114 in the LAL 100. This step can benecessary to lock in the specific shape of the LAL 100 by de-activatingall remaining photopolymerizable macromers still in the LAL 100, asdescribed, e.g., in the incorporated U.S. Pat. No. 6,905,641, to Plattet al, and in U.S. Pat. No. 7,281,795, to Sandstedt et al., amongothers.

FIG. 26 and FIGS. 27A-B illustrate an additional advantage of the method200. In some cases, the patient may ask the surgeon to form the CNAcentral region 110 in the implanted LAL 100, but after the procedure maybe dissatisfied with the outcome and demand a corrective procedure. Thiscan happen if the CNA central region 110 caused undesired ordisorienting blurriness, or halos, or both. Had the surgeon implanted anon-light-adjustable CNA IOL, such a patient demand would be impossibleto satisfy. In contrast, having implanted a blended LAL 100 enables thesurgeon to perform a “CNA erasure” process. The surgeon may perform anapplying 270 of a third illumination 272 to the LAL 100 with a thirdillumination pattern 274 centered on the central axis 112 to reduce theposition-dependent central optical power 114, induced in by the secondillumination 242 in the central region 110 of the LAL 100. FIG. 27A,left panel re-describes the LAL 100 as formed by the steps 210-260 ofthe method 200. FIG. 27A, right panel illustrates that performing of theadditional applying step 270 of the third illumination 272 to reduce thecentral optical power 114. This reduction is captured, e.g., in that theoptical power change 136 between the central optical power 114 and theperipheral optical power 124 is visibly reduced by the applying 270 ofthe third illumination 272. FIG. 27A, central panel shows a thirdillumination pattern 274 that is intense in the peripheral annulus 120but has low intensity in the central region 110, and therefore can besuitable for the applying 270 of the third illumination 272.

FIG. 27B illustrates that the applying the third illumination 272 canlargely restore the patient's visual acuity. The plot shows anoften-used measure of visual acuity, the Modulation Transfer Function,or MTF, as a function of its natural variable, the frequency, measuredin line pairs per mm, or lp/mm. Visibly, the MTF gets reduced from itsvalue prior to the second illumination 242 that formed the CNA centralregion 110 to lower values after the second illumination 242, since theCNA central region 110, while it improves the patient's near vision, italso enhances optical various aberrations. The reduction is morepronounced at higher frequencies. Importantly, the plot demonstratesthat the MTF can be restored to essentially the pre-second-illuminationlevels by applying of the third illumination 272.

In some embodiments, after the second illumination 242 the patient maybe dissatisfied with the outcome and demand a corrective procedure, butwith an opposite goal. The patient may report to the doctor no visualacuity problems caused by the CNA central region 110, but instead mayfind that not enough power was added. In such cases, the thirdillumination 272 may be used with a third illumination pattern 274 toenhance the central optical power 114 in the central region 110.

FIG. 28 illustrates a method 300 of adjusting the Light Adjustable Lens(LAL) 100, related to the method 200. The method 300 can comprise thefollowing steps.

-   -   Implanting 310 a LAL 100 into an eye, the LAL 100 having a        pre-molded position-dependent peripheral optical power 124 in at        least a peripheral annulus 120, centered on an annulus axis 122;    -   Determining 320 a central region 110 and a corresponding central        axis 112 of the LAL 100; and    -   Applying 330 a central illumination 342 to the LAL 100 with a        central illumination pattern 344 to induce a position-dependent        central optical power 114 in the central region 110 of the LAL        100; wherein    -   (340) The central axis 112 is laterally shifted relative to the        annulus axis 122, and    -   (350) An average of the central optical power 114 is at least        0.5 diopters different from than an average of the peripheral        optical power 124.

A difference between the method 200 and this method 300 is the manner inwhich the position dependent peripheral optical power 124 is formed. Inthe method 200, the peripheral optical power 124 is formed by theapplying 220 of the first illumination 222 to the already implanted LAL100. In contrast, in the method 300, this same peripheral optical power124 is pre-formed, prior to the implantation of the LAL 100, during themolding process of the manufacture of the LAL 100. A benefit of themethod 200 is that the positioning and the magnitude of the peripheralannulus 120 can be adjusted based on a measurement of the postsurgicalshifts of the LAL 100. Another benefit is that the magnitude andposition dependence of the peripheral optical power 124 can becustomized to the individual need of the specific patient. A drawbackcan be that doing so may require an additional procedure, with thenecessary scheduling and organization and an extra trip for the patient.(It is noted that this demand can be reduced in some cases by performingthe applying step 220 and the applying step 240 during a single visit bythe patient. This may require accelerating the iris 5 returning to itsnon-dilated state by pharmacological means.)

In contrast, benefits of the method 300 include that it starts with aLAL 100 that already has a pre-molded position-dependent peripheraloptical power 124. In a sense, this method 300 starts with an EDOF LAL,and the method concentrates on adding a CNA to this EDOF LAL. Therefore,the method 300 does not require the applying 220 of the firstillumination 222, and thus has one less procedure step. Thisbeneficially reduces the number of office visits for the patient.Potential drawbacks include that the positioning of the peripheralannulus 120 and the magnitude of the peripheral optical power 124 maynot be adjusted in response to a measurement of the postsurgical shiftof the LAL 100.

However, simple geometric considerations suggest that the total opticalpower accommodation necessary to mitigate presbyopia, i.e. to cover therange from near targets (d=0.4-0.5 m, i.e. 2-2.5 D) to distance targets(approx. 0 D) is about 2-2.5 D. This is to be delivered by thecombination of the higher central optical power 114 of the CNA centralregion 110 and the position-dependent variation of the EDOF peripheraloptical power 124. Therefore, embodiments of the LAL 100 that combine apre-molded optical power 124 with a radial variation of 0.5-1 D with acustomized addition of 1-2D of central optical power 114post-implantation, may be able to deliver all the benefits of theblended CNA-EDOF LAL designs, even without customizing the peripheraloptical power 124 by applying 220 the first illumination 222post-implantation. Moreover, surgeons may be provided with a series ofLALs with different amounts of radial peripheral optical powervariations, and thus different SAs, pre-molded into them. This mayenable the surgeon to select a LAL with the pre-molded SA and positiondependent peripheral optical power 124 that is most suitable for thepatient's individual need. All in all, both the method 200 and themethod 300 have advantages and drawbacks, and the surgeon may decidebetween them based on the needs of the individual patient.

Regarding the physical realization of the pre-molded EDOF LALs, theposition dependence of the peripheral optical power 124 can bepre-molded on the front of the LAL 100, on its back, or in combinationboth in the front and in the back.

All aspects of the blended LALs 100 shown in FIGS. 13-23, and allaspects of the method 200 shown in FIGS. 24-27, can be combined withembodiments of the method 300. One aspect is mentioned specifically: notonly the position variation of the peripheral optical power 124 can bepre-molded, but potentially a cylinder can be also pre-molded into theLAL 100,

FIG. 29 illustrates that the above two methods, method 200 and method300 can be thought of as subcases of a more generally articulated method400 of adjusting the Light Adjustable Lens (LAL) 100. The generalizedmethod 400 can comprise the following steps.

-   -   Causing 410 an LAL 100, implanted into an eye, to induce a first        depth of focus in an ophthalmic optical system, i.e. the optical        system of the eye with its cornea and the implanted LAL 100;    -   Determining 420 a central region 110 and a corresponding central        axis 112 of the LAL 100; and    -   Illuminating 430 the LAL 100 with an illumination pattern 434        centered on the central axis 112 to induce a second depth of        focus the ophthalmic optical system; wherein    -   (440) the central axis 112 is laterally shifted relative to a        LAL axis 102, and    -   (450) the second depth of focus is at least 0.5 diopters greater        than the first depth of focus.

Steps 420-450 can be analogous to the steps 230-260 of the method 200,with appropriate modifications in the last step. In addition, in someembodiments, the causing step 410 can include the applying 220 of thefirst illumination 222 to the LAL 100, in analogy to step 220 of themethod 200. In other embodiments, the causing step 410 can includeproviding a LAL 100 with a pre-molded depth of focus, in analogy to step310 of method 300. The pre-molded depth of focus can be induced by aposition-dependent peripheral optical power 124 in the peripheralannulus 120, centered on the annulus axis 122. Finally, in someembodiments the causing step 410 may involve a combination of the steps220 and 310.

As before, all aspects of the blended LALs 100 shown in FIGS. 13-23, allaspects of the method 200 shown in FIGS. 24-27, and all aspects of themethod 300 shown in FIG. 28 can be combined with embodiments of themethod 400.

FIG. 30 illustrates a method 500 of adjusting the Light Adjustable Lens(LAL) 100, primarily as shown in FIG. 22. The method 500 can include thefollowing steps.

-   -   Implanting 510 a LAL 100 b, having a LAL axis 102 b, into an        eye; and    -   Applying 520 an illumination 522 to the LAL 100 b with an        illumination pattern 524 to induce a position-dependent adjusted        optical power 314 in a light-adjusted region 310 r, centered on        an adjustment axis 312; wherein    -   (530) the adjustment axis 312 is laterally shifted relative to        the LAL axis 102 b.

As before, all aspects of the blended LALs 100 shown in FIGS. 13-23, allaspects of the methods 200/300/400 shown in FIGS. 24-29 can be combinedwith embodiments of the method 500.

Although the present invention and its advantages have been described indetail, it should be understood that various changes, substitutions andalterations can be made herein without departing from the spirit andscope of the invention as defined by the appended claims. Moreover, thescope of the present application is not intended to be limited to theparticular embodiments of the process, machine, manufacture, compositionof matter, means, methods and steps described in the specification. Asone of ordinary skill in the art will readily appreciate from thedisclosure of the present invention, processes, machines, manufacture,compositions of matter, means, methods, or steps, presently existing orlater to be developed that perform substantially the same function orachieve substantially the same result as the corresponding embodimentsdescribed herein may be utilized according to the present invention.Accordingly, the appended claims are intended to include within theirscope such processes, machines, manufacture, compositions of matter,means, methods, or steps.

While this document contains many specifics, details and numericalranges, these should not be construed as limitations of the scope of theinvention and of the claims, but, rather, as descriptions of featuresspecific to particular embodiments of the invention. Certain featuresthat are described in this document in the context of separateembodiments can also be implemented in combination in a singleembodiment. Conversely, various features that are described in thecontext of a single embodiment can also be implemented in multipleembodiments separately or in any suitable subcombination. Moreover,although features may be described above as acting in certaincombinations and even initially claimed as such, one or more featuresfrom a claimed combination can in some cases be excised from thecombination, and the claimed combination may be directed to anothersubcombination or a variation of a subcombinations.

REFERENCES

All patents and publications mentioned in the specification areindicative of the level of those skilled in the art to which theinvention pertains. All patents and publications are herein incorporatedby reference in their entirety to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference.

Patents

-   U.S. Pat. No. 4,260,725.-   U.S. Pat. No. 5,225,858.-   U.S. Pat. No. 5,236,970.-   U.S. Pat. No. 5,278,258.-   U.S. Pat. No. 5,376,694.-   U.S. Pat. No. 5,444,106.

Publications

-   Camellin M, Calossi A. A new formula for intraocular lens power    calculation after refractive corneal surgery. J Refract Surg. 2006;    22(2):187-99.-   Chokshi A R, Latkany R A, Speaker M G, Yu G. Intraocular lens    calculations after hyperopic refractive surgery. Ophthalmology.    2007; 104(11):2044-9.-   Ciuffreda; Accommodation, the Pupil, and Presbyopia, Chapter 4 in    Borisch's Clinical Refraction pp. 77-120, W. B. Saunders Company    (1998).-   E. J. Fernandez, S. Manzanera, P. Piers, P. Artal; Adaptive Optics    Visual Simulator”, J.-   Refract. Surg., 2002; 18: S634-S638.-   Ellingson, F. T.; Explanation of 3M Diffractive Intraocular    Lenses, J. Cataract and Refractive Surgery, 1990; 16: 697-701.-   Fain H B, Lim K L. A comparative analysis of intraocular lens power    calculation methods after myopic excimer laser surgery. J Refract    Surg. 2008; 24:355-360.-   Feiz V, Moshirfar M, Mannis M J, Reilly C D, Garcia-Ferrer F, Caspar    J J, Lim M C. Nomogram-based intraocular lens power adjustment after    myopic photorefractive keratectomy and LASIK. Ophthalmology 2005;    112:1381-1387.-   Hansen, T. E., Corydon, L., Krag, S., and Thim, K., New Muhifocal    Intraocular Lens Design, J. Cataract and Refractive Surgery, 1990;    16:38-41.-   Helmholtz, H., Treatise on Physiological Optics (translated by    Sohthall J PC), New York: Dover. (1969).-   Jin G C, Crandall A S, Jones J J. Intraocular lens exchange due to    incorrect lens power. Ophthalmology. 2007; 114:417-424.-   Latkany R A, Chokshi A R, Speaker M G, Abramson J, Soloway B D,    Yu G. Intraocular lens calculations after refractive surgery. J    Cataract Refract Surg. 2005; 31:562-570.-   Mackool R J, Ko W, Mackool R. Intraocular lens power calculation    after laser in situ keratomileusis: aphakic refraction technique. J    Cataract Refract Surg. 2006; 32:435-437.-   Mamalis N, Brubaker J, David D, Espandar L, Werner L. Complications    of foldable intraocular lenses requiring explantation or secondary    intervention—2007 survey update. J Cataract Refract Surg. 2008;    34:1584-1591.-   Murphy C, Tuft S J, Minassian D C. Refractive error and visual    outcome after cataract extraction. J Cataract Refract Surg. 2002;    28(1):62-66.-   Narvaez J, Zimmerman G, Stulting R D, Chang D H. Accuracy of    intraocular lens power prediction using the Hoffer Q, Holladay 1,    Holladay 2, and SRK/T formulas. J Cataract Refract Surg. 2006;    32:2050-2053.-   Olsen T. Sources of error in intraocular-lens power calculation. J    Cataract Refract Surg. 1992; 18:125-129.-   Packer M, Brown L K, Hoffman R S, Fine I H. Intraocular lens power    calculation after incisional and thermal keratorefractive surgery. J    Cataract Refract Surg. 2004; 30:1430-1434.-   Packer, M.; Fine, I. H.; Hoffman, R. S., Refractive Lens Exchange    with the Array Multifocal Intraocular Lens, H., J. Cataract and    Refract Surgery, 2002; 28:421-424.-   Preussner P R, Wahl J, Weitzel D, Berthold S, Kriechbaum K, Findl O.    Predicting postoperative intraocular lens position and    refraction. J. Cataract Refract Surg. 2004; 30:2077-2083.-   Steiner, R. F., Aler, B. L., Trentacost, D. J., Smith, P J.,    Taratino, N. A., A Prospective Comparative Study of the AMO Array    zonal-progressive multifocal silicone intraocular lens and a    monofocal intraocular lens, Opthalmology, 1999; 106(7): 1243-1255.-   Sun, X. Y.; Vicary, D.; Montgomery, P.; Griffiths, M. Toric    intraocular lenses for correcting astigmatism in 130 eyes.    Ophthalmology, 2000; 107(9); 1776-81.-   Thibos, L. N.; Hong, X.; Bradley, A.; Applegate, R. A, Accuracy and    Precision of Objective Refraction from Wavefront Aberrations,    Journal of Vision, 2004; 4: 329-351.-   Wang L, Booth M A, Koch D D. Comparison of intraocular lens power    calculation methods in eyes that have undergone LASIK. Ophthalmology    2004; 111:1825-1831.

1. A Light Adjustable Lens (LAL), comprising: a central region, centeredon a central axis, having a position-dependent central optical power;and a peripheral annulus, centered on an annulus axis and surroundingthe central region, having a position-dependent peripheral opticalpower, wherein an average of the central optical power is at least 0.5diopters different from an average of the peripheral optical power, andthe central axis is laterally shifted relative to the annulus axis. 2.The LAL of claim 1, wherein: the average of the central optical power isat least 1.0 diopter different from the average of the peripheraloptical power.
 3. The LAL of claim 1, wherein: the average of thecentral optical power is at least 0.5 diopter higher than the average ofthe peripheral optical power.
 4. The LAL of claim 1, wherein: theaverage of the central optical power is at least 0.5 diopter lower thanthe average of the peripheral optical power.
 5. The LAL of claim 1,comprising: a transition, between the central region and the peripheralannulus, having a transition optical power that changes from the centraloptical power to the peripheral optical power.
 6. The LAL of claim 5,wherein: the transition is a sharp boundary; and the central region andthe peripheral annulus meet at the sharp boundary.
 7. The LAL of claim5, wherein: the transition is a transition annulus between the centralregion and the peripheral annulus; wherein a ratio of a radial width ofthe transition to an outer radius of the transition is less than 0.5. 8.The LAL of claim 1, wherein: the central optical power has anapproximately flat position-dependence, having an optical powervariation less than 0.2 diopters over 50% of the central region.
 9. TheLAL of claim 1, wherein: the central optical power is a function of aradius from the central axis, having an optical power variation greaterthan 0.2 diopters over 50% of the central region.
 10. The LAL of claim1, wherein: the peripheral optical power has an approximately flatposition-dependence, having an optical power variation less than 0.2diopters over 50% of the peripheral annulus.
 11. The LAL of claim 1,wherein: a spherical aberration caused by the position-dependence of oneof the peripheral optical power, and a combination of the centraloptical power, the peripheral optical power, and a transition opticalpower, is in a range of −0.05 μm to −1 μm at a diameter of 4 mm in aplane of the LAL.
 12. The LAL of claim 1, wherein: a sphericalaberration caused by the position-dependence of one of the peripheraloptical power, and a combination of the central optical power, theperipheral optical power, and a transition optical power, is in a rangeof −0.05 μm to −0.35 μm at a diameter of 4 mm in a plane of the LAL. 13.The LAL of claim 1, wherein: a spherical aberration caused by theposition-dependence of one of the peripheral optical power, and acombination of the central optical power, the peripheral optical power,and a transition optical power, is in a range of −0.05 μm to −2 μm at adiameter of 6 mm in a corneal plane of an eye upon an implantation ofthe LAL in the eye.
 14. The LAL of claim 1, wherein: a sphericalaberration caused by the position-dependence of one of the peripheraloptical power, and a combination of the central optical power, theperipheral optical power, and a transition optical power, is in a rangeof −0.1μm to −0.6 μm at a diameter of 6 mm in a corneal plane of an eyeupon an implantation of the LAL in the eye.
 15. The LAL of claim 1,wherein: a spherical aberration caused by the position-dependence of atleast one of the central optical power and the peripheral optical poweris selected to approximately compensate a spherical aberration of acornea of the eye.
 16. The LAL of claim 1, wherein: a radius of thecentral region is in the range of 0.5 mm to 1.0 mm.
 17. The LAL of claim1, wherein: at least one of the position-dependent central optical powerand the position dependent peripheral optical power involves a cylinderangular dependence.
 18. A Light Adjustable Lens (LAL), comprising: alight-adjusted region, centered on an adjustment axis and having aposition-dependent adjusted optical power; wherein the adjustment axisis laterally shifted relative to a LAL axis of the LAL.